首页 > 最新文献

Journal of Steroid Biochemistry and Molecular Biology最新文献

英文 中文
Ligand-independent homo-/hetero-dimerization events of ERα and ERβ occur in the cytoplasmic compartment: Evidences from receptor dynamics in live cells
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-27 DOI: 10.1016/j.jsbmb.2024.106668
Ayushi Chhabra, Anjali Tripathi, Sheeba Rizvi, Rakesh K. Tyagi
Estrogen receptor α/β (ERα/β), are members of the steroid/nuclear receptor superfamily. They function as a ligand-inducible transcriptional regulator and are targets for the treatment of several endocrine diseases. Irrespective of the ligand binding status, ERα/β are primarily localized in the nucleus. However, when activated, they bind to specific DNA response elements as homo-/hetero-dimers to transactivate their target genes. Homo-/hetero-dimerization of ERα/β is crucial in ER-mediated regulation of gene expression and cellular responses. However, the cellular site that hosts the receptor homo-/hetero-dimerization, essential for its physiological function, is poorly explored. Here, using a comprehensive approach, we show that the initial intermolecular interaction between ERα/β monomers occurs in the cytoplasmic compartment of the cell in a ligand-independent manner. To explore the site of homo-/hetero-dimerization of ERα/β in living cells, we created GFP-ERα/β and mCherry-ERα constructs to perform co-receptor interaction studies through fluorescence microscopy and live-cell imaging. The study revealed that ERα/β monomers dimerize in the cytoplasmic compartment, facilitating the nuclear import of the complex. We also observed that ligand-independent homodimerization requires a functional nuclear localization signal in at least one of the ER monomers. Finally, it has also been shown that the ligand-binding domain of ERα plays a key role in ligand-independent homodimerization. Understanding the intricacies of ER homo-/hetero-dimerization events and their disease-associated dysregulation paves the way for potential therapeutic interventions.
{"title":"Ligand-independent homo-/hetero-dimerization events of ERα and ERβ occur in the cytoplasmic compartment: Evidences from receptor dynamics in live cells","authors":"Ayushi Chhabra,&nbsp;Anjali Tripathi,&nbsp;Sheeba Rizvi,&nbsp;Rakesh K. Tyagi","doi":"10.1016/j.jsbmb.2024.106668","DOIUrl":"10.1016/j.jsbmb.2024.106668","url":null,"abstract":"<div><div>Estrogen receptor α/β (ERα/β), are members of the steroid/nuclear receptor superfamily. They function as a ligand-inducible transcriptional regulator and are targets for the treatment of several endocrine diseases. Irrespective of the ligand binding status, ERα/β are primarily localized in the nucleus. However, when activated, they bind to specific DNA response elements as homo-/hetero-dimers to transactivate their target genes. Homo-/hetero-dimerization of ERα/β is crucial in ER-mediated regulation of gene expression and cellular responses. However, the cellular site that hosts the receptor homo-/hetero-dimerization, essential for its physiological function, is poorly explored. Here, using a comprehensive approach, we show that the initial intermolecular interaction between ERα/β monomers occurs in the cytoplasmic compartment of the cell in a ligand-independent manner. To explore the site of homo-/hetero-dimerization of ERα/β in living cells, we created GFP-ERα/β and mCherry-ERα constructs to perform co-receptor interaction studies through fluorescence microscopy and live-cell imaging. The study revealed that ERα/β monomers dimerize in the cytoplasmic compartment, facilitating the nuclear import of the complex. We also observed that ligand-independent homodimerization requires a functional nuclear localization signal in at least one of the ER monomers. Finally, it has also been shown that the ligand-binding domain of ERα plays a key role in ligand-independent homodimerization. Understanding the intricacies of ER homo-/hetero-dimerization events and their disease-associated dysregulation paves the way for potential therapeutic interventions.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106668"},"PeriodicalIF":2.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143154566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of programmed cell death in mammalian ovarian follicular atresia 程序性细胞死亡在哺乳动物卵巢卵泡闭锁中的作用。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-24 DOI: 10.1016/j.jsbmb.2024.106667
Huaming Xi, Xinyu Chen, Xianglong Wang, Feng Jiang, Dong Niu
Programmed cell death (PCD) is a fundamental process in the development process of organisms, including apoptosis, autophagy, ferroptosis, and pyroptosis. In mammalian ovaries, 99 % of follicles undergo atresia, while only 1 % mature and ovulate, which limits the reproductive efficiency of mammals. The PCD process is closely related to the regulation of follicle development and atresia. Recently, an increasing number of studies have reported that autophagy, pyroptosis, and ferroptosis of PCD are involved in regulating granulosa cell apoptosis and follicular atresia. Granulosa cell apoptosis is a hallmark of follicular atresia. Therefore, an understanding of molecular mechanisms regulating PCD events is required for future advances in the diagnosis and management of various disorders of follicular atresia. This review summarizes recent work on apoptosis, autophagy, pyroptosis, and ferroptosis of PCD that affect granulosa cell survival and follicular atresia, and further elucidating the mechanisms of follicular atresia and providing new directions for improving the reproductive capacity of humans and animals.
细胞程序性死亡(Programmed cell death, PCD)是生物发育过程中的一个基本过程,包括细胞凋亡、自噬、铁死亡和焦亡。在哺乳动物卵巢中,99% %的卵泡闭锁,而只有1% %的卵泡成熟并排卵,这限制了哺乳动物的生殖效率。PCD过程与卵泡发育和闭锁的调控密切相关。近年来,越来越多的研究报道PCD的自噬、焦亡和铁亡参与调控颗粒细胞凋亡和滤泡闭锁。颗粒细胞凋亡是滤泡闭锁的标志。因此,了解调节PCD事件的分子机制对于未来各种卵泡闭锁疾病的诊断和治疗是必要的。本文综述了近年来PCD细胞凋亡、自噬、焦亡和铁亡对颗粒细胞存活和卵泡闭锁的影响,并进一步阐明了卵泡闭锁的机制,为提高人和动物的生殖能力提供了新的研究方向。
{"title":"Role of programmed cell death in mammalian ovarian follicular atresia","authors":"Huaming Xi,&nbsp;Xinyu Chen,&nbsp;Xianglong Wang,&nbsp;Feng Jiang,&nbsp;Dong Niu","doi":"10.1016/j.jsbmb.2024.106667","DOIUrl":"10.1016/j.jsbmb.2024.106667","url":null,"abstract":"<div><div>Programmed cell death (PCD) is a fundamental process in the development process of organisms, including apoptosis, autophagy, ferroptosis, and pyroptosis. In mammalian ovaries, 99 % of follicles undergo atresia, while only 1 % mature and ovulate, which limits the reproductive efficiency of mammals. The PCD process is closely related to the regulation of follicle development and atresia. Recently, an increasing number of studies have reported that autophagy, pyroptosis, and ferroptosis of PCD are involved in regulating granulosa cell apoptosis and follicular atresia. Granulosa cell apoptosis is a hallmark of follicular atresia. Therefore, an understanding of molecular mechanisms regulating PCD events is required for future advances in the diagnosis and management of various disorders of follicular atresia. This review summarizes recent work on apoptosis, autophagy, pyroptosis, and ferroptosis of PCD that affect granulosa cell survival and follicular atresia, and further elucidating the mechanisms of follicular atresia and providing new directions for improving the reproductive capacity of humans and animals.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106667"},"PeriodicalIF":2.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular characterization of archival adrenal tumor tissue from patients with ACTH-independent Cushing syndrome acth非依赖性库欣综合征患者档案肾上腺肿瘤组织的分子特征。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-19 DOI: 10.1016/j.jsbmb.2024.106666
Juilee Rege , Aaron M. Udager
Cushing syndrome represents a multitude of signs and symptoms associated with long-term and excessive exposure to glucocorticoids. Solitary cortisol-producing adenomas (CPAs) account for most cases of ACTH-independent Cushing syndrome (CS). Technological advances in next-generation sequencing have significantly increased our understanding about the genetic landscape of CPAs. However, the conventional approach utilizes fresh/frozen tissue samples, which are not routinely available for most clinical adrenal adenoma specimens. This coupled with the fact that CS is relatively rare reduces the accessibility to CPAs for research. In order to circumvent this issue, our group recently developed a sequencing strategy that allowed the use of formalin-fixed paraffin-embedded (FFPE) CPA samples for mutation analysis. Our streamlined approach includes the visualization and genomic DNA (gDNA) capture of the cortisol-producing regions in the tumor using immunohistochemistry (IHC)-guided techniques followed by targeted and/or whole-exome sequencing analysis. This approach has the advantage of using both prospective and retrospective CPA cohorts since FFPE pathologic specimens are routinely banked. This review discusses this advanced approach using IHC-guided gDNA capture of pathologic tissue followed by NGS as a preferred method for mutational analysis of CPAs.
库欣综合征表现出与长期和过度接触糖皮质激素相关的多种体征和症状。孤立性皮质醇生成腺瘤(CPAs)占acth非依赖性库欣综合征(CS)的大多数病例。新一代测序技术的进步大大增加了我们对cpa基因景观的了解。然而,传统的方法使用新鲜/冷冻组织样本,这不是大多数临床肾上腺腺瘤标本的常规方法。再加上CS相对罕见的事实,减少了注册会计师进行研究的可及性。为了规避这个问题,我们的团队最近开发了一种测序策略,允许使用福尔马林固定石蜡包埋(FFPE) CPA样本进行突变分析。我们的简化方法包括使用免疫组织化学(IHC)引导技术对肿瘤中皮质醇产生区域进行可视化和基因组DNA (gDNA)捕获,然后进行靶向和/或全外显子组测序分析。该方法具有前瞻性和回顾性CPA队列的优点,因为FFPE病理标本是常规储存的。这篇综述讨论了这种先进的方法,使用ihc引导的病理组织gDNA捕获,然后使用NGS作为cpa突变分析的首选方法。
{"title":"Molecular characterization of archival adrenal tumor tissue from patients with ACTH-independent Cushing syndrome","authors":"Juilee Rege ,&nbsp;Aaron M. Udager","doi":"10.1016/j.jsbmb.2024.106666","DOIUrl":"10.1016/j.jsbmb.2024.106666","url":null,"abstract":"<div><div>Cushing syndrome represents a multitude of signs and symptoms associated with long-term and excessive exposure to glucocorticoids. Solitary cortisol-producing adenomas (CPAs) account for most cases of ACTH-independent Cushing syndrome (CS). Technological advances in next-generation sequencing have significantly increased our understanding about the genetic landscape of CPAs. However, the conventional approach utilizes fresh/frozen tissue samples, which are not routinely available for most clinical adrenal adenoma specimens. This coupled with the fact that CS is relatively rare reduces the accessibility to CPAs for research. In order to circumvent this issue, our group recently developed a sequencing strategy that allowed the use of formalin-fixed paraffin-embedded (FFPE) CPA samples for mutation analysis. Our streamlined approach includes the visualization and genomic DNA (gDNA) capture of the cortisol-producing regions in the tumor using immunohistochemistry (IHC)-guided techniques followed by targeted and/or whole-exome sequencing analysis. This approach has the advantage of using both prospective and retrospective CPA cohorts since FFPE pathologic specimens are routinely banked. This review discusses this advanced approach using IHC-guided gDNA capture of pathologic tissue followed by NGS as a preferred method for mutational analysis of CPAs.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106666"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anticancer effects of alpha-lipoic acid, a potent organosulfur compound by modulating matrix metalloproteinases and apoptotic markers in osteosarcoma MG-63 cells α -硫辛酸是一种有效的有机硫化合物,通过调节MG-63骨肉瘤细胞的基质金属蛋白酶和凋亡标记物的抗癌作用。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-16 DOI: 10.1016/j.jsbmb.2024.106664
Abdolreza Ahmadi , Fatemehsadat Hosseini , Mehdi Rostami , Mohammad Soukhtanloo
Osteosarcoma (OS), an extremely aggressive form of bone tumor primarily affects young adults. Despite significant advancements in clinical trials, the ability of cancer cells to metastasize and resist apoptosis remains a major challenge. To address these issues, novel therapeutic interventions with high specificity for these processes are essential. Alpha-lipoic acid (ALA), an organosulfur compound derived from octanoic acid, possesses a range of pharmacological properties. This study hypothesizes that ALA would inhibit metastasis and induce cell apoptosis in OS. To evaluate the potential of ALA, its effects on the migration, metastasis, and cell cycle of MG-63 OS cells were assessed, along with its ability to trigger apoptosis. To these aims, MG-63 cells were exposed to varying concentrations of ALA, and cell viability was measured using the alamarBlue assay. The impact of ALA on cell cycle progression, apoptosis, migration, and metastasis was analyzed through flow cytometry, scratch assay, and gelatin zymography. After validating the expression of MMP2, MMP9, VEGF, VEGFR, BAX, BCL-2, and P53 by the GEO database, the expression levels of these genes were examined through quantitative PCR (qPCR). Eventually, molecular docking was employed to simulate the interactions between ALA and matrix metalloproteinase (MMPs). The results demonstrated that ALA significantly inhibited cell migration, induced cell cycle arrest, and promoted apoptosis by upregulating P53 and BAX expression while downregulating BCL-2 levels. Furthermore, ALA was found to suppress the activity and expression of MMP2 and MMP9 and reduce the expression of angiogenesis markers. Notably, ALA interacted directly with the active site of MMP2 and MMP9. These findings suggest that ALA has the potential to be a promising agent with anti-cancer effects on MG-63 cells, warranting further preclinical investigations.
骨肉瘤(OS)是一种极具侵袭性的骨肿瘤,主要影响年轻人。尽管临床试验取得了重大进展,但癌细胞转移和抵抗细胞凋亡的能力仍然是一个重大挑战。为了解决这些问题,对这些过程具有高特异性的新型治疗干预措施是必不可少的。α -硫辛酸(ALA)是一种从辛酸中提取的有机硫化合物,具有一系列药理特性。本研究假设ALA可抑制肿瘤转移并诱导肿瘤细胞凋亡。为了评估ALA的潜力,我们评估了其对MG-63 OS细胞迁移、转移和细胞周期的影响,以及其引发细胞凋亡的能力。为此,MG-63细胞暴露于不同浓度的ALA中,并使用alamarBlue测定细胞活力。通过流式细胞术、划痕实验和明胶酶谱分析ALA对细胞周期进程、凋亡、迁移和转移的影响。通过GEO数据库验证MMP2、MMP9、VEGF、VEGFR、BAX、BCL-2、P53的表达后,通过定量PCR (qPCR)检测这些基因的表达水平。最后,利用分子对接模拟ALA与基质金属蛋白酶(matrix metalloproteinase, MMPs)之间的相互作用。结果表明,ALA通过上调P53和BAX表达,下调BCL-2水平,显著抑制细胞迁移,诱导细胞周期阻滞,促进细胞凋亡。此外,ALA还抑制了MMP2和MMP9的活性和表达,降低了血管生成标志物的表达。值得注意的是,ALA直接与MMP2和MMP9的活性位点相互作用。这些发现表明ALA有潜力成为一种对MG-63细胞具有抗癌作用的有前景的药物,值得进一步的临床前研究。
{"title":"Anticancer effects of alpha-lipoic acid, a potent organosulfur compound by modulating matrix metalloproteinases and apoptotic markers in osteosarcoma MG-63 cells","authors":"Abdolreza Ahmadi ,&nbsp;Fatemehsadat Hosseini ,&nbsp;Mehdi Rostami ,&nbsp;Mohammad Soukhtanloo","doi":"10.1016/j.jsbmb.2024.106664","DOIUrl":"10.1016/j.jsbmb.2024.106664","url":null,"abstract":"<div><div>Osteosarcoma (OS), an extremely aggressive form of bone tumor primarily affects young adults. Despite significant advancements in clinical trials, the ability of cancer cells to metastasize and resist apoptosis remains a major challenge. To address these issues, novel therapeutic interventions with high specificity for these processes are essential. Alpha-lipoic acid (ALA), an organosulfur compound derived from octanoic acid, possesses a range of pharmacological properties. This study hypothesizes that ALA would inhibit metastasis and induce cell apoptosis in OS. To evaluate the potential of ALA, its effects on the migration, metastasis, and cell cycle of MG-63 OS cells were assessed, along with its ability to trigger apoptosis. To these aims, MG-63 cells were exposed to varying concentrations of ALA, and cell viability was measured using the alamarBlue assay. The impact of ALA on cell cycle progression, apoptosis, migration, and metastasis was analyzed through flow cytometry, scratch assay, and gelatin zymography. After validating the expression of <em>MMP2</em>, <em>MMP9</em>, <em>VEGF</em>, <em>VEGFR</em>, <em>BAX</em>, <em>BCL-2</em>, and <em>P53</em> by the GEO database, the expression levels of these genes were examined through quantitative PCR (qPCR). Eventually, molecular docking was employed to simulate the interactions between ALA and matrix metalloproteinase (MMPs). The results demonstrated that ALA significantly inhibited cell migration, induced cell cycle arrest, and promoted apoptosis by upregulating <em>P53</em> and <em>BAX</em> expression while downregulating <em>BCL-2</em> levels. Furthermore, ALA was found to suppress the activity and expression of MMP2 and MMP9 and reduce the expression of angiogenesis markers. Notably, ALA interacted directly with the active site of MMP2 and MMP9. These findings suggest that ALA has the potential to be a promising agent with anti-cancer effects on MG-63 cells, warranting further preclinical investigations.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106664"},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of combined exposure to 17α-methyltestosterone and polystyrene microplastics on lipid metabolism and the nervous system in Danio rerio 17α-甲基睾酮和聚苯乙烯微塑料复合暴露对小鼠脂质代谢和神经系统的影响
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-16 DOI: 10.1016/j.jsbmb.2024.106665
Tongyao Li , Gen Chen , Lu Cao , Weiya Rong , Haiyan Zhao , Zijun Xiong , Qing Liu , Jing Song , Weiwei Wang , Yu Liu , Xianzong Wang , Shaozhen Liu
Polystyrene (PS) microplastics are pervasive environmental pollutants that are harmful to aquatic organisms upon degradation. The synthetic androgen 17α-methyltestosterone (MT) is an environmental endocrine-disrupting chemical. This study aimed to systematically evaluate the combined histological and molecular effects of MT and PS exposure on the liver and brain tissues of Danio rerio with focus on lipid metabolism and neural function disruption. Female D. rerio were exposed to 50 ng/L MT and 0.5 mg/L PS (5 μm in diameter) for 21 d. Histological observations, real-time quantitative PCR (qPCR), and RNA-sequencing (RNA-seq) analysis were employed to assess the effects of PS and MT. These results indicated that MT and PS co-exposure caused fatty degeneration of liver cells and a significant upregulation of lipid synthesis-related genes (ACSS1, CEL, FASN, and GK5). In brain tissue, the observed effects included reduced marginal layer neuron counts, cytoplasmic loosening of central layer neurons, disordered gray matter layer cells, and vascular congestion. RNA-seq analysis further revealed significant enrichment of differentially expressed genes in the “glycine, serine, and threonine metabolism” and “neuroactive ligand-receptor interaction” signaling pathways. Thus, MT and PS co-exposure induced lipid metabolism disorders in D. rerio and influence neural signaling by altering the “neuroactive ligand-receptor interaction” pathway. These findings highlight the complex risks posed by environmental pollutants to aquatic life and provide critical insights for environmental protection and aquatic health research.
聚苯乙烯(PS)微塑料是普遍存在的环境污染物,降解后对水生生物有害。合成雄激素17α-甲基睾酮(MT)是一种环境内分泌干扰化学物质。本研究旨在系统评价MT和PS暴露对斑马鱼肝脏和脑组织的组织学和分子综合影响,重点关注脂质代谢和神经功能破坏。将雌鼠分别暴露于50ng/L MT和0.5mg/L PS(直径5 μm)中21 d,采用组织学观察、实时定量PCR (qPCR)和rna测序(RNA-seq)分析评估PS和MT的影响。结果表明,MT和PS共暴露导致肝细胞脂肪变性,脂质合成相关基因(ACSS1、CEL、FASN和GK5)显著上调。在脑组织中,观察到的影响包括边缘层神经元计数减少,中央层神经元细胞质松动,灰质层细胞紊乱和血管充血。RNA-seq分析进一步揭示了“甘氨酸、丝氨酸和苏氨酸代谢”和“神经活性配体-受体相互作用”信号通路中差异表达基因的显著富集。因此,MT和PS共同暴露诱导了D. rerio的脂质代谢紊乱,并通过改变“神经活性配体-受体相互作用”途径影响神经信号传导。这些发现突出了环境污染物对水生生物构成的复杂风险,并为环境保护和水生健康研究提供了重要见解。
{"title":"Effects of combined exposure to 17α-methyltestosterone and polystyrene microplastics on lipid metabolism and the nervous system in Danio rerio","authors":"Tongyao Li ,&nbsp;Gen Chen ,&nbsp;Lu Cao ,&nbsp;Weiya Rong ,&nbsp;Haiyan Zhao ,&nbsp;Zijun Xiong ,&nbsp;Qing Liu ,&nbsp;Jing Song ,&nbsp;Weiwei Wang ,&nbsp;Yu Liu ,&nbsp;Xianzong Wang ,&nbsp;Shaozhen Liu","doi":"10.1016/j.jsbmb.2024.106665","DOIUrl":"10.1016/j.jsbmb.2024.106665","url":null,"abstract":"<div><div>Polystyrene (PS) microplastics are pervasive environmental pollutants that are harmful to aquatic organisms upon degradation. The synthetic androgen 17α-methyltestosterone (MT) is an environmental endocrine-disrupting chemical. This study aimed to systematically evaluate the combined histological and molecular effects of MT and PS exposure on the liver and brain tissues of <em>Danio rerio</em> with focus on lipid metabolism and neural function disruption. Female <em>D. rerio</em> were exposed to 50 ng/L MT and 0.5 mg/L PS (5 μm in diameter) for 21 d. Histological observations, real-time quantitative PCR (qPCR), and RNA-sequencing (RNA-seq) analysis were employed to assess the effects of PS and MT. These results indicated that MT and PS co-exposure caused fatty degeneration of liver cells and a significant upregulation of lipid synthesis-related genes (<em>ACSS1, CEL, FASN,</em> and <em>GK5</em>). In brain tissue, the observed effects included reduced marginal layer neuron counts, cytoplasmic loosening of central layer neurons, disordered gray matter layer cells, and vascular congestion. RNA-seq analysis further revealed significant enrichment of differentially expressed genes in the “glycine, serine, and threonine metabolism” and “neuroactive ligand-receptor interaction” signaling pathways. Thus, MT and PS co-exposure induced lipid metabolism disorders in <em>D. rerio</em> and influence neural signaling by altering the “neuroactive ligand-receptor interaction” pathway. These findings highlight the complex risks posed by environmental pollutants to aquatic life and provide critical insights for environmental protection and aquatic health research.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106665"},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
1,25-(OH)2D3 improves SD rats high-altitude pulmonary edema by inhibiting ferroptosis and ferritinophagy in alveolar epithelial cells 1,25(OH)2D3通过抑制肺泡上皮细胞铁下垂和铁蛋白吞噬改善SD大鼠高原肺水肿。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-15 DOI: 10.1016/j.jsbmb.2024.106663
Yaxuan Wang , Hong Su , Xue Lin , Chongyang Dai , Qian Cheng , Zhangchang Deng , Yangyang yang , Xiaoyan Pu

Background

This study investigates the protective effects and potential mechanisms of 1,25-(OH)2D3 against high-altitude pulmonary edema (HAPE).

Methods

Hypoxia-induced rats were administered 1,25-(OH)2D3 for 24, 48, and 72 hours, and we observed lung tissue injury and pulmonary edema. Immunohistochemistry (IHC) and Western blot analyses were employed to analyze the expression of markers associated with ferroptosis and ferritinophagy in rat lungs. Metabolomics analysis was conducted to investigate changes in serum lipid metabolites. We validated the mechanism of action of 1,25-(OH)2D3 in type II alveolar epithelial cells induced by hypoxia.

Results

Our results demonstrated that hypoxic exposure significantly altered sodium-water transport in the lungs, leading to edema formation. The degree of pulmonary edema was most pronounced at 48 hours of hypoxi. Treatment with 1,25-(OH)2D3 improved lung function and reduced the degree of pulmonary edema in hypoxic rats. Hypoxia-induced increases in 4-HNE and MDA levels in the lungs, along with iron accumulation, were observed. Hypoxia also resulted in elevated levels of NCOA4, LC3Ⅱ, and FTH1 proteins in the lungs. Furthermore, treatment with 1,25-(OH)2D3 significantly inhibited ferroptosis and ferritinophagy in the lungs after hypoxia. The levels of lipid metabolites, such as L-Aspartic acid and L-Fucose, were significantly elevated in the serum of hypoxic rats. After 1,25-(OH)2D3 treatment, these levels exhibited a significant reduction.

Conclusion

In hypoxic type II alveolar epithelial cells, 1,25-(OH)2D3 improved hypoxia-induced sodium-water transport, ferroptosis, and ferritinophagy, which were reversed by the autophagy agonist Rapamycin.By modulating ferroptosis and ferritinophagy, 1,25-(OH)2D3 mitigated the deleterious effects of hypoxia on pulmonary function.
背景:本研究旨在探讨1,25(OH)2D3对高原肺水肿(HAPE)的保护作用及其可能机制。方法:缺氧诱导大鼠给予1,25(OH)2D3 24、48、72小时,观察肺组织损伤和肺水肿。采用免疫组化(IHC)和免疫印迹(Western blot)方法分析大鼠肺中铁中毒和铁蛋白吞噬相关标志物的表达。代谢组学分析研究血清脂质代谢物的变化。我们验证了1,25(OH)2D3在缺氧诱导的II型肺泡上皮细胞中的作用机制。结果:我们的研究结果表明,低氧暴露显著改变了肺中的钠-水运输,导致水肿的形成。肺水肿程度在缺氧48小时时最为明显。用1,25(OH)2D3治疗可改善缺氧大鼠的肺功能,降低肺水肿程度。观察到缺氧诱导的肺中4-HNE和MDA水平的增加,以及铁的积累。缺氧也导致肺部NCOA4、LC3Ⅱ和FTH1蛋白水平升高。此外,用1,25(OH)2D3治疗可显著抑制缺氧后肺中的铁下垂和铁蛋白吞噬。缺氧大鼠血清中L-天冬氨酸、L-焦糖等脂质代谢产物水平明显升高。在1,25(OH)2D3处理后,这些水平显着降低。结论:在缺氧II型肺泡上皮细胞中,1,25(OH)2D3可改善缺氧诱导的钠-水转运、铁凋亡和铁蛋白自噬,而自噬激动剂雷帕霉素可逆转这一作用。1,25(OH)2D3通过调节铁下垂和铁蛋白吞噬,减轻缺氧对肺功能的有害影响。
{"title":"1,25-(OH)2D3 improves SD rats high-altitude pulmonary edema by inhibiting ferroptosis and ferritinophagy in alveolar epithelial cells","authors":"Yaxuan Wang ,&nbsp;Hong Su ,&nbsp;Xue Lin ,&nbsp;Chongyang Dai ,&nbsp;Qian Cheng ,&nbsp;Zhangchang Deng ,&nbsp;Yangyang yang ,&nbsp;Xiaoyan Pu","doi":"10.1016/j.jsbmb.2024.106663","DOIUrl":"10.1016/j.jsbmb.2024.106663","url":null,"abstract":"<div><h3>Background</h3><div>This study investigates the protective effects and potential mechanisms of 1,25-(OH)<sub>2</sub>D<sub>3</sub> against high-altitude pulmonary edema (HAPE).</div></div><div><h3>Methods</h3><div>Hypoxia-induced rats were administered 1,25-(OH)<sub>2</sub>D<sub>3</sub> for 24, 48, and 72 hours, and we observed lung tissue injury and pulmonary edema. Immunohistochemistry (IHC) and Western blot analyses were employed to analyze the expression of markers associated with ferroptosis and ferritinophagy in rat lungs. Metabolomics analysis was conducted to investigate changes in serum lipid metabolites. We validated the mechanism of action of 1,25-(OH)<sub>2</sub>D<sub>3</sub> in type II alveolar epithelial cells induced by hypoxia.</div></div><div><h3>Results</h3><div>Our results demonstrated that hypoxic exposure significantly altered sodium-water transport in the lungs, leading to edema formation. The degree of pulmonary edema was most pronounced at 48 hours of hypoxi. Treatment with 1,25-(OH)<sub>2</sub>D<sub>3</sub> improved lung function and reduced the degree of pulmonary edema in hypoxic rats. Hypoxia-induced increases in 4-HNE and MDA levels in the lungs, along with iron accumulation, were observed. Hypoxia also resulted in elevated levels of NCOA4, LC3Ⅱ, and FTH1 proteins in the lungs. Furthermore, treatment with 1,25-(OH)<sub>2</sub>D<sub>3</sub> significantly inhibited ferroptosis and ferritinophagy in the lungs after hypoxia. The levels of lipid metabolites, such as L-Aspartic acid and L-Fucose, were significantly elevated in the serum of hypoxic rats. After 1,25-(OH)<sub>2</sub>D<sub>3</sub> treatment, these levels exhibited a significant reduction.</div></div><div><h3>Conclusion</h3><div>In hypoxic type II alveolar epithelial cells, 1,25-(OH)<sub>2</sub>D<sub>3</sub> improved hypoxia-induced sodium-water transport, ferroptosis, and ferritinophagy, which were reversed by the autophagy agonist Rapamycin.By modulating ferroptosis and ferritinophagy, 1,25-(OH)<sub>2</sub>D<sub>3</sub> mitigated the deleterious effects of hypoxia on pulmonary function.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106663"},"PeriodicalIF":2.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vitamin D deficiency in Mongolian men aged 15–49 years 蒙古 15-49 岁男性维生素 D 缺乏症。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-10 DOI: 10.1016/j.jsbmb.2024.106656
Tserendolgor Uush
We aimed to estimate the prevalence of vitamin D deficiency in Mongolian men aged from 15 to 49 years at the National level as part of the Fifth National Nutrition Survey in 2016. This was a cross-sectional survey, conducted between September and November in 21 aimags of 4 economic regions of the country, and also in Ulaanbaatar. Given the regional differences in lifestyle and nutritional status, the target populations were stratified into 5 strata based on their economic region and in Ulaanbaatar, with equal samples drawn from each stratum using a cluster-randomized sampling design. A representative sample of 30 clusters [villages] was randomly selected using Probability Proportional to Size [PPS] methodology in each of the 4 regions and in Ulaanbaatar for a total of 150 cluster units. The selection of survey participants differed for the three sampling regions. Household eligibility was based on having a child 0–59 months of age, living in the household which was randomly selected from each cluster for a total of 450 households in each region. Households with a child 0–59 months of age were selected from household lists available at the kheseg or bagh level. All men 15–49 years of age who resided in the selected households were also eligible to participate in the survey. Serum concentration of 25-hydroxyvitamin D [25(OH)D] were measured using an enzyme-linked fluorescence assay in 377 men aged 15–49 years. The overall mean serum level of 25(OH)D concentration was 22.26 ± 0.48 ng/mL (95 % CI 21.31–23.21). The mean serum 25(OH)D concentrations were 19.65 ± 0.32 ng/mL (95 % CI19.01–19.82), and 33.68 ± 0.49 ng/mL (95 % CI 32.72–34.64) in vitamin D deficient, and in vitamin D sufficient subjects, respectively. The prevalence of vitamin D deficiency was 83.5 % with no significant difference in the prevalence of vitamin D deficiency by age group, economic region, area, location, education, and wealth index quintile. The prevalence of men in this study who were overweight or obese was 48.8 % and 14.6 % respectively. Although no significant difference was found between vitamin D deficiency and obesity, vitamin D deficiency was higher among men aged 30–39 and 40–49 years old by age specific analyses. The men did not take vitamin D supplements, and there is currently no vitamin D food fortification in Mongolia. The findings of this survey showed that vitamin D deficiency in men is a public health problem in Mongolia. In conclusion, vitamin D deficiency are common in Mongolian men, which indicates the need for vitamin D screening and treatment, as well as for an increased use of vitamin D supplements and for implementing vitamin D food fortification programs.
作为2016年第五次全国营养调查的一部分,我们的目的是在全国范围内估计15至49岁蒙古男性维生素D缺乏症的患病率。这是一项横断面调查,于9月至11月在该国4个经济区的21个地区进行,也在乌兰巴托进行。考虑到生活方式和营养状况的区域差异,在乌兰巴托,根据目标人群的经济区域将其分为5个阶层,每个阶层采用整群随机抽样设计抽取等量样本。在这4个地区和乌兰巴托,使用大小比例概率(PPS)方法随机选择了30个集群[村庄]的代表性样本,共150个集群单位。调查对象的选择在三个抽样地区有所不同。家庭资格的基础是有一个0-59个月大的孩子,住在从每个地区450个家庭的每组随机选择的家庭中。从可在kheseg或bagh一级获得的家庭名单中选择有0-59个月儿童的家庭。居住在选定家庭中的所有15-49岁的男子也有资格参加调查。采用酶联荧光法测定377例15-49岁男性血清25-羟基维生素D [25(OH)D]浓度。总体平均血清25(OH)D浓度水平为22.26±0.48ng/ml (95% CI 21.31 ~ 23.21)。维生素D缺乏组和维生素D充足组的平均血清25(OH)D浓度分别为19.65±0.32ng/ml (95% CI19.01 ~ 19.82)和33.68±0.49ng/ml (95% CI 32.72 ~ 34.64)。维生素D缺乏症患病率为83.5%,不同年龄段、经济区域、地区、地理位置、教育程度、财富指数五分位数的维生素D缺乏症患病率差异无统计学意义。本研究中超重或肥胖的男性患病率分别为48.8%和14.6%。虽然维生素D缺乏和肥胖之间没有显著差异,但根据年龄分析,维生素D缺乏在30-39岁和40-49岁的男性中更高。这些人没有服用维生素D补充剂,而蒙古目前也没有维生素D食品强化。调查结果表明,蒙古男性缺乏维生素D是一个公共卫生问题。总之,维生素D缺乏症在蒙古男性中很常见,这表明需要对维生素D进行筛查和治疗,以及增加维生素D补充剂的使用和实施维生素D食品强化计划。(摘要共378字)。
{"title":"Vitamin D deficiency in Mongolian men aged 15–49 years","authors":"Tserendolgor Uush","doi":"10.1016/j.jsbmb.2024.106656","DOIUrl":"10.1016/j.jsbmb.2024.106656","url":null,"abstract":"<div><div>We aimed to estimate the prevalence of vitamin D deficiency in Mongolian men aged from 15 to 49 years at the National level as part of the Fifth National Nutrition Survey in 2016. This was a cross-sectional survey, conducted between September and November in 21 aimags of 4 economic regions of the country, and also in Ulaanbaatar. Given the regional differences in lifestyle and nutritional status, the target populations were stratified into 5 strata based on their economic region and in Ulaanbaatar, with equal samples drawn from each stratum using a cluster-randomized sampling design. A representative sample of 30 clusters [villages] was randomly selected using Probability Proportional to Size [PPS] methodology in each of the 4 regions and in Ulaanbaatar for a total of 150 cluster units. The selection of survey participants differed for the three sampling regions. Household eligibility was based on having a child 0–59 months of age, living in the household which was randomly selected from each cluster for a total of 450 households in each region. Households with a child 0–59 months of age were selected from household lists available at the kheseg or bagh level. All men 15–49 years of age who resided in the selected households were also eligible to participate in the survey. Serum concentration of 25-hydroxyvitamin D [25(OH)D] were measured using an enzyme-linked fluorescence assay in 377 men aged 15–49 years. The overall mean serum level of 25(OH)D concentration was 22.26 ± 0.48 ng/mL (95 % CI 21.31–23.21). The mean serum 25(OH)D concentrations were 19.65 ± 0.32 ng/mL (95 % CI19.01–19.82), and 33.68 ± 0.49 ng/mL (95 % CI 32.72–34.64) in vitamin D deficient, and in vitamin D sufficient subjects, respectively. The prevalence of vitamin D deficiency was 83.5 % with no significant difference in the prevalence of vitamin D deficiency by age group, economic region, area, location, education, and wealth index quintile. The prevalence of men in this study who were overweight or obese was 48.8 % and 14.6 % respectively. Although no significant difference was found between vitamin D deficiency and obesity, vitamin D deficiency was higher among men aged 30–39 and 40–49 years old by age specific analyses. The men did not take vitamin D supplements, and there is currently no vitamin D food fortification in Mongolia. The findings of this survey showed that vitamin D deficiency in men is a public health problem in Mongolia. In conclusion, vitamin D deficiency are common in Mongolian men, which indicates the need for vitamin D screening and treatment, as well as for an increased use of vitamin D supplements and for implementing vitamin D food fortification programs.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106656"},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
1,25-dihydroxyvitamin D3 regulates enteroglial bioactivity through butyric acid pathway in a high-fat diet mouse model 1,25-二羟基维生素D3在高脂饮食小鼠模型中通过丁酸途径调节肠胶质生物活性。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-06 DOI: 10.1016/j.jsbmb.2024.106655
Aiwen Feng , Shaosheng Su , Qian Li , Cheng Li , Yingyan Liu , Jiasheng Qiu
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), affects enteric glial cells (EGCs) activity, but the mechanism is still unknown. The current study aimed to explore whether 1,25(OH)2D3 could regulate EGCs activity via butyrate pathway in a high-fat diet model. Male C57BL/6 J mice were fed with standard diet (SDD), or vitamin-D-deficient diet (VDD), or high-fat diet (HFD), or HFD plus sodium butyrate (SBR), or HFD plus 1,25(OH)2D3, or HFD plus S100B inhibitor ONO-2506 in vivo. CRL-2690 and Caco-2 cells were treated with palmitic acid (PA) and oleic acid (OA) complex, or S100B, or S100B plus butyric acid (BA) in vitro. 25(OH)D3, 1,25(OH)2D3, TNF-α and S100B concentrations were assayed by enzyme-linked immuno- sorbent assay (ELISA). Colonic mucosal permeability was measured by using FITC-dextran 4 kDa. Colonic butyrate was detected using high-performance liquid chromatography (HPLC). The results showed HFD decreased serum 25(OH)D3 and 1,25(OH)2D3 concentrations and colonic butyrate generation. 1,25(OH)2D3 supplementation raised butyrate production in the colon. 1,25(OH)2D3 and sodium butyrate supplementation inhibited EGCs to produce S100B and reduced colonic permeability to FITC-dextran. Inhibition of S100B pathway by ONO- 2506 decreased colonic hyperpermeability. In vitro experiments showed butyrate treatment not only reduced S100B and TNF-α secretion from PA/OA-treated CRL-2690 cells, but also decreased the permeability of S100B-treated Caco-2 cells. Collectively, 1,25(OH)2D3 elicited butyrate to suppress EGCs activation, which helped to prevent intestinal barrier injury.
1,25-二羟基维生素D3 (1,25(OH)2D3)影响肠胶质细胞(EGCs)活性,但其机制尚不清楚。本研究旨在探讨1,25(OH)2D3是否可以通过丁酸途径调节高脂饮食模型中EGCs的活性。雄性C57BL/6J小鼠在体内分别饲喂标准日粮(SDD)、维生素d缺乏日粮(VDD)、高脂日粮(HFD)、HFD加丁酸钠(SBR)、HFD加1,25(OH)2D3、HFD加S100B抑制剂ONO-2506。体外分别用棕榈酸(PA)和油酸(OA)复合物、S100B、S100B加丁酸(BA)处理CRL-2690和Caco-2细胞。采用酶联免疫吸附法(ELISA)检测25(OH)D3、1,25(OH)2D3、TNF-α和S100B浓度。采用fitc -葡聚糖4kDa测定结肠粘膜通透性。采用高效液相色谱法检测大肠丁酸盐。结果表明,HFD降低了血清25(OH)D3和1,25(OH)2D3浓度,降低了结肠丁酸盐的生成。补充1,25(OH)2D3提高了结肠中丁酸盐的产量。添加1,25(OH)2D3和丁酸钠抑制EGCs产生S100B,降低结肠对fitc -葡聚糖的通透性。ONO- 2506抑制S100B通路降低结肠高通透性。体外实验表明,丁酸处理不仅能降低PA/ oa处理的CRL-2690细胞分泌S100B和TNF-α,还能降低S100B处理的Caco-2细胞的通透性。总的来说,1,25(OH)2D3诱导丁酸抑制EGCs的激活,这有助于防止肠屏障损伤。
{"title":"1,25-dihydroxyvitamin D3 regulates enteroglial bioactivity through butyric acid pathway in a high-fat diet mouse model","authors":"Aiwen Feng ,&nbsp;Shaosheng Su ,&nbsp;Qian Li ,&nbsp;Cheng Li ,&nbsp;Yingyan Liu ,&nbsp;Jiasheng Qiu","doi":"10.1016/j.jsbmb.2024.106655","DOIUrl":"10.1016/j.jsbmb.2024.106655","url":null,"abstract":"<div><div>1,25-dihydroxyvitamin D3 (1,25(OH)2D3), affects enteric glial cells (EGCs) activity, but the mechanism is still unknown. The current study aimed to explore whether 1,25(OH)2D3 could regulate EGCs activity via butyrate pathway in a high-fat diet model. Male C57BL/6 J mice were fed with standard diet (SDD), or vitamin-D-deficient diet (VDD), or high-fat diet (HFD), or HFD plus sodium butyrate (SBR), or HFD plus 1,25(OH)2D3, or HFD plus S100B inhibitor ONO-2506 <em>in vivo</em>. CRL-2690 and Caco-2 cells were treated with palmitic acid (PA) and oleic acid (OA) complex, or S100B, or S100B plus butyric acid (BA) <em>in vitro</em>. 25(OH)D3, 1,25(OH)2D3, TNF-α and S100B concentrations were assayed by enzyme-linked immuno- sorbent assay (ELISA). Colonic mucosal permeability was measured by using FITC-dextran 4 kDa. Colonic butyrate was detected using high-performance liquid chromatography (HPLC). The results showed HFD decreased serum 25(OH)D3 and 1,25(OH)2D3 concentrations and colonic butyrate generation. 1,25(OH)2D3 supplementation raised butyrate production in the colon. 1,25(OH)2D3 and sodium butyrate supplementation inhibited EGCs to produce S100B and reduced colonic permeability to FITC-dextran. Inhibition of S100B pathway by ONO- 2506 decreased colonic hyperpermeability. <em>In vitro</em> experiments showed butyrate treatment not only reduced S100B and TNF-α secretion from PA/OA-treated CRL-2690 cells, but also decreased the permeability of S100B-treated Caco-2 cells. Collectively, 1,25(OH)2D3 elicited butyrate to suppress EGCs activation, which helped to prevent intestinal barrier injury.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106655"},"PeriodicalIF":2.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
APN/AdipoRon regulates luteal steroidogenesis through AMPK/EZH2/H3K27me3 in goats APN/AdipoRon通过AMPK/EZH2/H3K27me3调控山羊黄体甾体生成。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-06 DOI: 10.1016/j.jsbmb.2024.106653
Xiaomeng Pei, Haolin Li, Hao Yu, Wei Wang, Dagan Mao
AMPK plays a crucial role in cellular energy metabolism and is involved in the regulation of luteal steroidogenesis by APN and its analog AdipoRon. To further explore the regulatory mechanism of AMPK in goat luteal steroidogenesis mediated by APN, cyclic and pregnant CL were utilized to assess the localization and expression of AMPK, EZH2, H3K27me3 and H3K27ac by WB and mIHC, and the interaction between AMPK and EZH2 by Co-IP. Then, isolated luteal cells were treated with APN/AdipoRon to evaluate the expression levels of AMPK, EZH2, H3K27me3 and H3K27ac. Results showed that AMPK and EZH2 were co-localized to the cytoplasm of luteal cells, and interacted as detected by Co-IP. H3K27me3 and H3K27ac were localized to the nucleus of goat luteal cells. H3K27me3 expression in late CL was significantly higher than that in early and middle CL, while the expressions of AMPK, H3K27ac and EZH2 in middle CL were significantly higher than those in early and late CL. Notably, all these proteins were expressed at similar levels between pregnancy and middle cycle, with the exception of EZH2. Following incubation with AdipoRon (25 μM) and APN (1 μg/mL) for 24 h, the expressions of AMPK and H3K27ac decreased, while H3K27me3 increased in luteal cells. Compound C (AMPK activity inhibitor) reversed the AdipoRon - induced decrease in EZH2 expression and the increase in H3K27me3 expression. The increased H3K27me3 expression and decreased steroidogenic protein (CYP11A1 and HSD3B) expression after GSK126 (EZH2 inhibitor) treatment were consistent with the effects seen after AdipoRon treatment. In conclusion, APN/AdipoRon inhibits luteal steroidogenesis by inhibiting the interaction between AMPK and EZH2, thereby promoting H3K27me3 expression.
AMPK在细胞能量代谢中起着至关重要的作用,并参与APN及其类似物AdipoRon对黄体类固醇形成的调节。为了进一步探讨AMPK在APN介导的山羊黄体甾体生成中的调控机制,我们利用环周和妊娠CL分别通过WB和mIHC评估AMPK、EZH2、H3K27me3和H3K27ac的定位和表达,并通过Co-IP评估AMPK与EZH2的相互作用。然后,用APN/AdipoRon处理离体黄体细胞,评估AMPK、EZH2、H3K27me3和H3K27ac的表达水平。结果表明,AMPK和EZH2在黄体细胞胞浆中共定位,并通过Co-IP检测到相互作用。H3K27me3和H3K27ac定位于山羊黄体细胞核。H3K27me3在晚期CL中的表达显著高于早期和中期CL, AMPK、H3K27ac和EZH2在中期CL中的表达显著高于早期和晚期CL。值得注意的是,除EZH2外,所有这些蛋白在妊娠期和中期表达水平相似。AdipoRon (25μM)和APN (1μg/mL)作用24h后,黄体细胞AMPK和H3K27ac表达降低,H3K27me3表达升高。化合物C (AMPK活性抑制剂)逆转了AdipoRon诱导的EZH2表达的降低和H3K27me3表达的增加。GSK126 (EZH2抑制剂)处理后,H3K27me3表达增加,类固醇蛋白(CYP11A1和HSD3B)表达降低,与AdipoRon处理后的效果一致。综上所述,APN/AdipoRon通过抑制AMPK与EZH2的相互作用抑制黄体甾体生成,从而促进H3K27me3的表达。
{"title":"APN/AdipoRon regulates luteal steroidogenesis through AMPK/EZH2/H3K27me3 in goats","authors":"Xiaomeng Pei,&nbsp;Haolin Li,&nbsp;Hao Yu,&nbsp;Wei Wang,&nbsp;Dagan Mao","doi":"10.1016/j.jsbmb.2024.106653","DOIUrl":"10.1016/j.jsbmb.2024.106653","url":null,"abstract":"<div><div>AMPK plays a crucial role in cellular energy metabolism and is involved in the regulation of luteal steroidogenesis by APN and its analog AdipoRon. To further explore the regulatory mechanism of AMPK in goat luteal steroidogenesis mediated by APN, cyclic and pregnant CL were utilized to assess the localization and expression of AMPK, EZH2, H3K27me3 and H3K27ac by WB and mIHC, and the interaction between AMPK and EZH2 by Co-IP. Then, isolated luteal cells were treated with APN/AdipoRon to evaluate the expression levels of AMPK, EZH2, H3K27me3 and H3K27ac. Results showed that AMPK and EZH2 were co-localized to the cytoplasm of luteal cells, and interacted as detected by Co-IP. H3K27me3 and H3K27ac were localized to the nucleus of goat luteal cells. H3K27me3 expression in late CL was significantly higher than that in early and middle CL, while the expressions of AMPK, H3K27ac and EZH2 in middle CL were significantly higher than those in early and late CL. Notably, all these proteins were expressed at similar levels between pregnancy and middle cycle, with the exception of EZH2. Following incubation with AdipoRon (25 μM) and APN (1 μg/mL) for 24 h, the expressions of AMPK and H3K27ac decreased, while H3K27me3 increased in luteal cells. Compound C (AMPK activity inhibitor) reversed the AdipoRon - induced decrease in EZH2 expression and the increase in H3K27me3 expression. The increased H3K27me3 expression and decreased steroidogenic protein (CYP11A1 and HSD3B) expression after GSK126 (EZH2 inhibitor) treatment were consistent with the effects seen after AdipoRon treatment. In conclusion, APN/AdipoRon inhibits luteal steroidogenesis by inhibiting the interaction between AMPK and EZH2, thereby promoting H3K27me3 expression.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106653"},"PeriodicalIF":2.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of inhibition and eradication of bacterial biofilm by solasodin solasodin对细菌生物膜的抑制和根除效果评价。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-05 DOI: 10.1016/j.jsbmb.2024.106654
Ana Raquel Pereira da Silva , Maria do Socorro Costa , Nara Juliana Santos Araújo , Thiago Sampaio de Freitas , Cícera Laura Roque Paulo , Maria Anésia Sousa de Alencar , José Maria Barbosa-Filho , Jacqueline Cosmo Andrade-Pinheiro , Henrique Douglas Melo Coutinho
Biofilms are complex microbial structures that have a significant impact on human health, industry and the environment. These complex structures represent one of the main mechanisms of microbial resistance, and their development constitutes a serious health problem. Therefore, the aim of this study was to verify the potential for inhibition and eradication of bacterial biofilm by salosodine, which is a steroidal alkaloid sapogenin found in plants of the Solanum genus. The antibiotics gentamicin, norfloxacin, ampicillin and the antiseptic agent chlorhexidine gluconate were used as positive controls to compare the results. Solasodin showed significant results in inhibiting the formation of Enterococcus faecalis and Staphylococcus aureus biofilms at the two concentrations tested. And when comparing the effect of solasodine for the two concentrations and the effect of the antibiotic gentamicin, it was found that sapogenin showed a better percentage in inhibiting E. faecalis biofilm formation. And against Pseudomonas aeruginosa, solasodine only inhibited biofilm formation at the highest concentration compared to the control. In the biofilm eradication results, solasodine showed a significant reduction in the biomass of the S. aureus biofilm, and when compared with the percentage reduction of the antibiotics, solasodine showed a relevant result for both concentrations. Only at the lowest concentration did solasodine show a reduction in P. aeruginosa biofilm biomass, a reduction close to that of chlorhexidine gluconate. In terms of activity, solasodine has been shown to have the potential to inhibit biofilm formation. However, further tests are needed to investigate the mechanisms of action of this sapogenin on the bacterial biofilms tested.
生物膜是一种复杂的微生物结构,对人类健康、工业和环境产生重大影响。这些复杂的结构代表了微生物耐药性的主要机制之一,它们的发展构成了严重的健康问题。因此,本研究的目的是验证salosodine对细菌生物膜的抑制和根除的潜力,salosodine是一种在茄属植物中发现的甾体生物碱皂苷元。以抗生素庆大霉素、诺氟沙星、氨苄西林和抗菌药物葡萄糖酸氯己定为阳性对照,比较结果。在两种浓度下,Solasodin对粪肠球菌和金黄色葡萄球菌生物膜的形成均有明显的抑制作用。通过比较两种浓度的索拉索定和抗生素庆大霉素的效果,发现皂苷元对粪肠球菌生物膜形成的抑制效果更好。对铜绿假单胞菌,索拉索丁仅抑制生物膜的形成,且浓度最高。在生物膜根除结果中,solasodine显示出金黄色葡萄球菌生物膜生物量的显著减少,并且与抗生素的减少百分比相比,solasodine在两种浓度下都显示出相关的结果。只有在最低浓度下,索拉索定才显示出铜绿假单胞菌生物膜生物量的减少,其减少量接近葡萄糖酸氯己定。就活性而言,solasodine已被证明具有抑制生物膜形成的潜力。然而,需要进一步的试验来研究这种皂苷元对细菌生物膜的作用机制。
{"title":"Evaluation of inhibition and eradication of bacterial biofilm by solasodin","authors":"Ana Raquel Pereira da Silva ,&nbsp;Maria do Socorro Costa ,&nbsp;Nara Juliana Santos Araújo ,&nbsp;Thiago Sampaio de Freitas ,&nbsp;Cícera Laura Roque Paulo ,&nbsp;Maria Anésia Sousa de Alencar ,&nbsp;José Maria Barbosa-Filho ,&nbsp;Jacqueline Cosmo Andrade-Pinheiro ,&nbsp;Henrique Douglas Melo Coutinho","doi":"10.1016/j.jsbmb.2024.106654","DOIUrl":"10.1016/j.jsbmb.2024.106654","url":null,"abstract":"<div><div>Biofilms are complex microbial structures that have a significant impact on human health, industry and the environment. These complex structures represent one of the main mechanisms of microbial resistance, and their development constitutes a serious health problem. Therefore, the aim of this study was to verify the potential for inhibition and eradication of bacterial biofilm by salosodine, which is a steroidal alkaloid sapogenin found in plants of the <em>Solanum</em> genus. The antibiotics gentamicin, norfloxacin, ampicillin and the antiseptic agent chlorhexidine gluconate were used as positive controls to compare the results. Solasodin showed significant results in inhibiting the formation of <em>Enterococcus faecalis</em> and <em>Staphylococcus aureus</em> biofilms at the two concentrations tested. And when comparing the effect of solasodine for the two concentrations and the effect of the antibiotic gentamicin, it was found that sapogenin showed a better percentage in inhibiting <em>E. faecalis</em> biofilm formation. And against <em>Pseudomonas aeruginosa</em>, solasodine only inhibited biofilm formation at the highest concentration compared to the control. In the biofilm eradication results, solasodine showed a significant reduction in the biomass of the <em>S. aureus</em> biofilm, and when compared with the percentage reduction of the antibiotics, solasodine showed a relevant result for both concentrations. Only at the lowest concentration did solasodine show a reduction in <em>P. aeruginosa</em> biofilm biomass, a reduction close to that of chlorhexidine gluconate. In terms of activity, solasodine has been shown to have the potential to inhibit biofilm formation. However, further tests are needed to investigate the mechanisms of action of this sapogenin on the bacterial biofilms tested.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106654"},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Steroid Biochemistry and Molecular Biology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1