首页 > 最新文献

Biological Research最新文献

英文 中文
General regulatory factors exert differential effects on nucleosome sliding activity of the ISW1a complex 一般调控因子对 ISW1a 复合物的核小体滑动活性产生不同影响
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-04 DOI: 10.1186/s40659-024-00500-6
Andrea Oyarzún-Cisterna, Cristián Gidi, Fernanda Raiqueo, Roberto Amigo, Camila Rivas, Marcela Torrejón, José L. Gutiérrez
Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown. Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome. Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.
染色质动态与转录调控等需要访问 DNA 的过程密切相关。参与基因调控区染色质动态的因子包括一般调控因子(GRFs)。这些因子有助于建立和维持核糖体缺失区(NDR)。这些区域通过组蛋白沉积和核小体滑动由核小体填充,后者由包括 ISW1a 在内的多种 ATP 依赖性染色质重塑复合物催化。据观察,GRFs 可作为阻止核小体滑向 NDRs 的屏障。然而,目前还不清楚不同 GRFs 阻碍滑动活动的相对能力。有鉴于此,我们对主要的 GRFs 进行了比较分析,重点分析它们调节 ISW1a 介导的核小体滑动的能力。在核小体重塑实验中测试的 GRFs 中,Rap1 是唯一能够阻碍 ISW1a 活性的因子。这种作用要求 Rap1 的同源序列位于连接体上,而连接体在核小体重塑过程中成为入口 DNA。此外,在八聚体转移试验中,Rap1 还能阻碍核小体的组装。同时,与测试的其他 GRF 相比,Rap1 对其目标序列的亲和力最高,停留时间最长。同样,通过对公开的全基因组数据进行生物信息学分析,我们发现体内核小体占据率和组蛋白沉积与 Rap1 对基因组中靶序列的亲和力成反比。我们的研究结果表明,DNA结合亲和力、停留时间和相对于核小体核心的特定翻译位置是GRFs的关键特征,它们在核小体滑动和组装中发挥着重要作用。
{"title":"General regulatory factors exert differential effects on nucleosome sliding activity of the ISW1a complex","authors":"Andrea Oyarzún-Cisterna, Cristián Gidi, Fernanda Raiqueo, Roberto Amigo, Camila Rivas, Marcela Torrejón, José L. Gutiérrez","doi":"10.1186/s40659-024-00500-6","DOIUrl":"https://doi.org/10.1186/s40659-024-00500-6","url":null,"abstract":"Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown. Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome. Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841093","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
The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells 糖尿病对间充质干细胞分化为胰岛素分泌细胞的影响
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-02 DOI: 10.1186/s40659-024-00502-4
Omar I. Badr, Mohamed M. Kamal, Shohda A. El-Maraghy, Heba R. Ghaiad
Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro. We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and diabetic-Ad-MSCs (DM-Ad-MSCs) into IPCs was compared morphologically then through determining the gene expression of β-cell markers including neurogenin-3 (Ngn-3), homeobox protein (Nkx6.1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and insulin-1 (Ins-1) and eventually, through performing glucose-stimulated insulin secretion test (GSIS). Finally, the therapeutic potential of N-Ad-MSCs and DM-Ad-MSCs transplantation was compared in vivo in STZ-induced diabetic animals. Our results showed no significant difference in the characteristics of N-Ad-MSCs and DM-Ad-MSCs. However, we demonstrated a significant difference in their abilities to differentiate into IPCs in vitro morphologically in addition to β-cell markers expression, and functional assessment via GSIS test. Furthermore, the abilities of both Ad-MSCs to control hyperglycemia in diabetic rats in vivo was assessed through measuring fasting blood glucose (FBGs), body weight (BW), histopathological examination of both pancreas and liver and immunoexpression of insulin in pancreata of study groups. Our findings reveal the effectiveness of N-Ad-MSCs in differentiating into IPCs in vitro and controlling the hyperglycemia of STZ-induced diabetic rats in vivo compared to DM-Ad-MSCs.
糖尿病(DM)是一种全球性流行病,发病率不断上升。糖尿病是一种与慢性高血糖有关的代谢性疾病。除了传统治疗方法外,迄今为止还没有临床认可的治疗糖尿病的方法。将间充质干细胞(MSCs)分化为胰岛素分泌细胞(IPCs)是治疗DM的一种很有前景的方法。我们的研究旨在探讨DM对间充质干细胞在体内和体外分化为IPCs的影响。我们从正常大鼠和 STZ 诱导的糖尿病 Sprague-Dawley 雄性大鼠的附睾脂肪中分离出脂肪间充质干细胞(Ad-MSCs)。随后,比较了正常-Ad-间充质干细胞(N-Ad-MSCs)和糖尿病-Ad-间充质干细胞(DM-Ad-MSCs)在体外分化成 IPCs 的形态学结果,并通过测定神经原蛋白-3(Ngn-3)、同工酶蛋白(Nkx6.1)、肌肉神经纤维肉瘤癌基因同源物 A(MafA)和胰岛素-1(Ins-1)等β细胞标志物的基因表达,最后通过葡萄糖刺激胰岛素分泌试验(GSIS)进行检测。最后,在 STZ 诱导的糖尿病动物体内比较了 N-Ad-MSCs 和 DM-Ad-MSCs 移植的治疗潜力。结果显示,N-Ad-间充质干细胞和DM-Ad-间充质干细胞的特性没有明显差异。然而,我们发现它们在体外分化成 IPC 的能力除了在形态学上有显著差异外,在 β 细胞标志物表达和通过 GSIS 测试进行功能评估方面也有显著差异。此外,我们还通过测量研究组大鼠的空腹血糖(FBGs)、体重(BW)、胰腺和肝脏的组织病理学检查以及胰岛素在胰腺中的免疫表达,评估了两种 Ad-MSCs 在体内控制糖尿病大鼠高血糖的能力。我们的研究结果表明,与 DM-Ad-MSCs 相比,N-Ad-MSCs 能有效地在体外分化成 IPC,并控制 STZ 诱导的糖尿病大鼠体内的高血糖。
{"title":"The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells","authors":"Omar I. Badr, Mohamed M. Kamal, Shohda A. El-Maraghy, Heba R. Ghaiad","doi":"10.1186/s40659-024-00502-4","DOIUrl":"https://doi.org/10.1186/s40659-024-00502-4","url":null,"abstract":"Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro. We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and diabetic-Ad-MSCs (DM-Ad-MSCs) into IPCs was compared morphologically then through determining the gene expression of β-cell markers including neurogenin-3 (Ngn-3), homeobox protein (Nkx6.1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and insulin-1 (Ins-1) and eventually, through performing glucose-stimulated insulin secretion test (GSIS). Finally, the therapeutic potential of N-Ad-MSCs and DM-Ad-MSCs transplantation was compared in vivo in STZ-induced diabetic animals. Our results showed no significant difference in the characteristics of N-Ad-MSCs and DM-Ad-MSCs. However, we demonstrated a significant difference in their abilities to differentiate into IPCs in vitro morphologically in addition to β-cell markers expression, and functional assessment via GSIS test. Furthermore, the abilities of both Ad-MSCs to control hyperglycemia in diabetic rats in vivo was assessed through measuring fasting blood glucose (FBGs), body weight (BW), histopathological examination of both pancreas and liver and immunoexpression of insulin in pancreata of study groups. Our findings reveal the effectiveness of N-Ad-MSCs in differentiating into IPCs in vitro and controlling the hyperglycemia of STZ-induced diabetic rats in vivo compared to DM-Ad-MSCs. ","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841327","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
Control of astrocytic Ca2+ signaling by nitric oxide-dependent S-nitrosylation of Ca2+ homeostasis modulator 1 channels 一氧化氮依赖的钙离子平衡调节器 1 通道 S-亚硝基化对星形胶质细胞钙离子信号的控制
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-30 DOI: 10.1186/s40659-024-00503-3
Mariela Puebla, Manuel F. Muñoz, Mauricio A. Lillo, Jorge E. Contreras, Xavier F. Figueroa
Astrocytes Ca2+ signaling play a central role in the modulation of neuronal function. Activation of metabotropic glutamate receptors (mGluR) by glutamate released during an increase in synaptic activity triggers coordinated Ca2+ signals in astrocytes. Importantly, astrocytes express the Ca2+-dependent nitric oxide (NO)-synthetizing enzymes eNOS and nNOS, which might contribute to the Ca2+ signals by triggering Ca2+ influx or ATP release through the activation of connexin 43 (Cx43) hemichannels, pannexin-1 (Panx-1) channels or Ca2+ homeostasis modulator 1 (CALHM1) channels. Hence, we aim to evaluate the participation of NO in the astrocytic Ca2+ signaling initiated by stimulation of mGluR in primary cultures of astrocytes from rat brain cortex. Astrocytes were stimulated with glutamate or t-ACPD and NO-dependent changes in [Ca2+]i and ATP release were evaluated. In addition, the activity of Cx43 hemichannels, Panx-1 channels and CALHM1 channels was also analyzed. The expression of Cx43, Panx-1 and CALHM1 in astrocytes was confirmed by immunofluorescence analysis and both glutamate and t-ACPD induced NO-mediated activation of CALHM1 channels via direct S-nitrosylation, which was further confirmed by assessing CALHM1-mediated current using the two-electrode voltage clamp technique in Xenopus oocytes. Pharmacological blockade or siRNA-mediated inhibition of CALHM1 expression revealed that the opening of these channels provides a pathway for ATP release and the subsequent purinergic receptor-dependent activation of Cx43 hemichannels and Panx-1 channels, which further contributes to the astrocytic Ca2+ signaling. Our findings demonstrate that activation of CALHM1 channels through NO-mediated S-nitrosylation in astrocytes in vitro is critical for the generation of glutamate-initiated astrocytic Ca2+ signaling.
星形胶质细胞的 Ca2+ 信号在调节神经元功能方面发挥着核心作用。突触活动增加时释放的谷氨酸会激活代谢型谷氨酸受体(mGluR),从而触发星形胶质细胞中协调的 Ca2+ 信号。重要的是,星形胶质细胞表达依赖 Ca2+ 的一氧化氮(NO)合成酶 eNOS 和 nNOS,它们可能通过激活连接素 43(Cx43)半桥通道、pannexin-1(Panx-1)通道或 Ca2+ 平衡调节器 1(CALHM1)通道触发 Ca2+ 流入或 ATP 释放,从而促进 Ca2+ 信号。因此,我们旨在评估 NO 在大鼠大脑皮层星形胶质细胞原代培养物中参与由 mGluR 刺激引发的星形胶质细胞 Ca2+ 信号转导的情况。用谷氨酸或 t-ACPD 刺激星形胶质细胞,评估[Ca2+]i 和 ATP 释放的 NO 依赖性变化。此外,还分析了 Cx43 半通道、Panx-1 通道和 CALHM1 通道的活性。免疫荧光分析证实了 Cx43、Panx-1 和 CALHM1 在星形胶质细胞中的表达,谷氨酸和 t-ACPD 通过直接 S-亚硝基化诱导了 NO 介导的 CALHM1 通道活化。药理阻断或 siRNA 介导的 CALHM1 表达抑制显示,这些通道的开放为 ATP 释放以及随后嘌呤能受体依赖性激活 Cx43 半ich通道和 Panx-1 通道提供了途径,从而进一步促进了星形胶质细胞的 Ca2+ 信号转导。我们的研究结果表明,在体外星形胶质细胞中通过 NO 介导的 S-亚硝基化激活 CALHM1 通道对于谷氨酸引发的星形胶质细胞 Ca2+ 信号的产生至关重要。
{"title":"Control of astrocytic Ca2+ signaling by nitric oxide-dependent S-nitrosylation of Ca2+ homeostasis modulator 1 channels","authors":"Mariela Puebla, Manuel F. Muñoz, Mauricio A. Lillo, Jorge E. Contreras, Xavier F. Figueroa","doi":"10.1186/s40659-024-00503-3","DOIUrl":"https://doi.org/10.1186/s40659-024-00503-3","url":null,"abstract":"Astrocytes Ca2+ signaling play a central role in the modulation of neuronal function. Activation of metabotropic glutamate receptors (mGluR) by glutamate released during an increase in synaptic activity triggers coordinated Ca2+ signals in astrocytes. Importantly, astrocytes express the Ca2+-dependent nitric oxide (NO)-synthetizing enzymes eNOS and nNOS, which might contribute to the Ca2+ signals by triggering Ca2+ influx or ATP release through the activation of connexin 43 (Cx43) hemichannels, pannexin-1 (Panx-1) channels or Ca2+ homeostasis modulator 1 (CALHM1) channels. Hence, we aim to evaluate the participation of NO in the astrocytic Ca2+ signaling initiated by stimulation of mGluR in primary cultures of astrocytes from rat brain cortex. Astrocytes were stimulated with glutamate or t-ACPD and NO-dependent changes in [Ca2+]i and ATP release were evaluated. In addition, the activity of Cx43 hemichannels, Panx-1 channels and CALHM1 channels was also analyzed. The expression of Cx43, Panx-1 and CALHM1 in astrocytes was confirmed by immunofluorescence analysis and both glutamate and t-ACPD induced NO-mediated activation of CALHM1 channels via direct S-nitrosylation, which was further confirmed by assessing CALHM1-mediated current using the two-electrode voltage clamp technique in Xenopus oocytes. Pharmacological blockade or siRNA-mediated inhibition of CALHM1 expression revealed that the opening of these channels provides a pathway for ATP release and the subsequent purinergic receptor-dependent activation of Cx43 hemichannels and Panx-1 channels, which further contributes to the astrocytic Ca2+ signaling. Our findings demonstrate that activation of CALHM1 channels through NO-mediated S-nitrosylation in astrocytes in vitro is critical for the generation of glutamate-initiated astrocytic Ca2+ signaling.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841308","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
Increased levels and activation of the IL-17 receptor in microglia contribute to enhanced neuroinflammation in cerebellum of hyperammonemic rats 小胶质细胞中 IL-17 受体水平的升高和激活是高氨血症大鼠小脑神经炎症加剧的原因之一
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-27 DOI: 10.1186/s40659-024-00504-2
Yaiza M Arenas, Adrià López-Gramaje, C. Montoliu, M. Llansola, Vicente Felipo
{"title":"Increased levels and activation of the IL-17 receptor in microglia contribute to enhanced neuroinflammation in cerebellum of hyperammonemic rats","authors":"Yaiza M Arenas, Adrià López-Gramaje, C. Montoliu, M. Llansola, Vicente Felipo","doi":"10.1186/s40659-024-00504-2","DOIUrl":"https://doi.org/10.1186/s40659-024-00504-2","url":null,"abstract":"","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652175","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
Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis) 智利蓝贻贝(Mytilus chilensis)中两个类似蒸汽机的转座子的鉴定和表达分析
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-26 DOI: 10.1186/s40659-024-00498-x
Gloria Arriagada, Johan Quezada, Nicolas Merino-Veliz, Fernando Avilés, Diana Tapia-Cammas, Jorge Gomez, Daniela Curotto, Juan A. Valdes, Pablo A. Oyarzún, Cristian Gallardo-Escárate, Michael J. Metzger, Marco Alvarez
Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon.
播散性肿瘤病(DN)是双壳类软体动物循环系统的一种细胞增生性疾病。这种疾病可在个体间传播,也可由溴脱氧尿苷等外部化学物质诱发。我们克隆并鉴定了一种名为 Steamer 的 LTR 反转座子。Steamer mRNA水平和基因拷贝数与DN相关,可用作该疾病的标记。迄今为止,逆转录转座子的表达与 DN 有关的软体动物只有 Mya arenaria。另一方面,有报道称智利蓝贻贝(Mytilus chilensis)也会感染 DN。我们的目的是鉴定智利贻贝中的逆转录转座子,并研究它们在播散性肿瘤中的表达水平。在此,我们表明,2018 年 8 月从两个养殖区采集的个体中有 7.1%呈现出 DN 所描述的形态特征。利用Steamer序列询问M. chilensis的转录组,我们发现了两个推定的逆转录转座子,命名为Steamer样元件(MchSLEs)。MchSLEs 存在于 M. chilensis 的基因组中,而且 MchSLE1 确实是一个 LTR 逆转录转座子。所报道的 MchSLEs 的表达和拷贝数均与 DN 状态无关,但两者在不同动物个体中的表达水平不同。我们还报告说,在培养的 M. chilensis 血细胞中,溴脱氧尿苷可诱导 MchSLEs1 的表达。我们的结论是,存在于智利贻贝中的 SLEs 在不同个体中的表达量不同,而且与播散性肿瘤无关。用溴脱氧尿苷等应激源处理血细胞可诱导 MchSLE1 的表达,这表明在智利贻贝中,环境应激源可诱导 LTR 反转座子的活化。
{"title":"Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis)","authors":"Gloria Arriagada, Johan Quezada, Nicolas Merino-Veliz, Fernando Avilés, Diana Tapia-Cammas, Jorge Gomez, Daniela Curotto, Juan A. Valdes, Pablo A. Oyarzún, Cristian Gallardo-Escárate, Michael J. Metzger, Marco Alvarez","doi":"10.1186/s40659-024-00498-x","DOIUrl":"https://doi.org/10.1186/s40659-024-00498-x","url":null,"abstract":"Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140801070","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
Noncoding RNAs in skeletal development and disorders 骨骼发育和骨骼疾病中的非编码 RNA
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-22 DOI: 10.1186/s40659-024-00497-y
Qing Yao, Tailin He, Jian-You Liao, Rongdong Liao, Xiaohao Wu, Lijun Lin, Guozhi Xiao
Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as “junk DNA”. Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.
编码蛋白质的基因只占人类基因组总序列的不到 2%,98% 的遗传信息以前被称为 "垃圾 DNA"。与此同时,非编码 RNA(ncRNA)约占人类细胞转录输出的 60%。近几十年来,已经发现了数千种 ncRNA,它们在与增殖、分化、凋亡和新陈代谢等基本细胞过程相关的各种细胞通路中调控基因表达的重要作用已得到广泛研究。此外,它们形成的基因调控网络在正常发育和病理条件下调节基因表达。在这篇综述中,我们整合了当前关于 ncRNA 的分类、生物发生和功能的信息,以及这些 ncRNA 如何通过调控体内关键基因和信号通路来支持骨骼发育。我们还总结了与常见骨骼疾病和失调(包括但不限于骨质疏松症、骨关节炎、类风湿性关节炎、脊柱侧弯和椎间盘变性)有关的 ncRNA 的最新知识,重点介绍了这些 ncRNA 在体内、体外和体外研究中发挥的作用。
{"title":"Noncoding RNAs in skeletal development and disorders","authors":"Qing Yao, Tailin He, Jian-You Liao, Rongdong Liao, Xiaohao Wu, Lijun Lin, Guozhi Xiao","doi":"10.1186/s40659-024-00497-y","DOIUrl":"https://doi.org/10.1186/s40659-024-00497-y","url":null,"abstract":"Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as “junk DNA”. Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634361","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
Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage Cx43 半通道和 panx1 通道有助于乙醇诱导的星形胶质细胞功能障碍和损伤
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-04 DOI: 10.1186/s40659-024-00493-2
Gonzalo I. Gómez, Tanhia F. Alvear, Daniela A. Roa, Arantza Farias-Pasten, Sergio A. Vergara, Luis A. Mellado, Claudio J. Martinez-Araya, Juan Prieto-Villalobos, Claudia García-Rodríguez, Natalia Sánchez, Juan C. Sáez, Fernando C. Ortíz, Juan A. Orellana
Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1β and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.
酒精是一种被广泛滥用的药物,会大大降低生活质量,引发慢性疾病和精神问题,对健康、社会和经济造成严重影响。此前,我们曾证实,非自愿饮酒会增加青少年大鼠星形胶质细胞中 Cx43 半通道和 Panx1 通道的开放。然而,乙醇是否会直接影响星形胶质细胞半通道,如果会,这又会如何影响星形胶质细胞的功能和存活,这些问题仍有待阐明。临床相关浓度的乙醇会促进小鼠皮质星形胶质细胞中 Cx43 半通道和 Panx1 通道的开放,从而导致 ATP 和谷氨酸的释放。这些大孔通道的激活依赖于 Toll 样受体 4、P2X7 受体、IL-1β 和 TNF-α 信号、p38 丝裂原活化蛋白激酶和诱导型一氧化氮(NO)合酶。值得注意的是,乙醇诱导的 Cx43 半通道和 Panx1 通道开放会导致细胞因子分泌、NO 生成、神经胶质递质释放和星形胶质细胞反应性的改变,最终影响存活率。我们的研究揭示了乙醇损害星形胶质细胞功能的新机制,其中涉及炎症通路的连续刺激,而炎症通路会进一步增加 Cx43 半ich通道和 Panx1 通道的开放。我们假设,在各种酒精使用障碍的进展过程中,以星形胶质半通道为靶点可能是保护星形胶质细胞功能和突触可塑性的一种很有前景的药理学方法。
{"title":"Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage","authors":"Gonzalo I. Gómez, Tanhia F. Alvear, Daniela A. Roa, Arantza Farias-Pasten, Sergio A. Vergara, Luis A. Mellado, Claudio J. Martinez-Araya, Juan Prieto-Villalobos, Claudia García-Rodríguez, Natalia Sánchez, Juan C. Sáez, Fernando C. Ortíz, Juan A. Orellana","doi":"10.1186/s40659-024-00493-2","DOIUrl":"https://doi.org/10.1186/s40659-024-00493-2","url":null,"abstract":"Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1β and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591274","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
Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis 上皮-间质转化过程中的加连蛋白:促进组织修复、纤维化和癌症转移的作用和机制
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-04 DOI: 10.1186/s40659-024-00490-5
Elisa Perez-Moreno, Claudia Oyanadel, Adely de la Peña, Ronny Hernández, Francisca Pérez-Molina, Claudia Metz, Alfonso González, Andrea Soza
Galectins are soluble glycan-binding proteins that interact with a wide range of glycoproteins and glycolipids and modulate a broad spectrum of physiological and pathological processes. The expression and subcellular localization of different galectins vary among tissues and cell types and change during processes of tissue repair, fibrosis and cancer where epithelial cells loss differentiation while acquiring migratory mesenchymal phenotypes. The epithelial-mesenchymal transition (EMT) that occurs in the context of these processes can include modifications of glycosylation patterns of glycolipids and glycoproteins affecting their interactions with galectins. Moreover, overexpression of certain galectins has been involved in the development and different outcomes of EMT. This review focuses on the roles and mechanisms of Galectin-1 (Gal-1), Gal-3, Gal-4, Gal-7 and Gal-8, which have been involved in physiologic and pathogenic EMT contexts.
凝集素是一种可溶性糖结合蛋白,能与多种糖蛋白和糖脂相互作用,并能调节多种生理和病理过程。在组织修复、纤维化和癌变过程中,上皮细胞会失去分化能力,同时获得迁移性间充质表型,不同组织和细胞类型的上皮细胞会失去分化能力,同时获得迁移性间充质表型。在这些过程中发生的上皮-间充质转化(EMT)可能包括糖脂和糖蛋白糖基化模式的改变,从而影响它们与半连接蛋白的相互作用。此外,某些 galectins 的过度表达也与 EMT 的发展和不同结果有关。本综述将重点讨论 Galectin-1(Gal-1)、Gal-3、Gal-4、Gal-7 和 Gal-8 在生理性和致病性 EMT 中的作用和机制。
{"title":"Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis","authors":"Elisa Perez-Moreno, Claudia Oyanadel, Adely de la Peña, Ronny Hernández, Francisca Pérez-Molina, Claudia Metz, Alfonso González, Andrea Soza","doi":"10.1186/s40659-024-00490-5","DOIUrl":"https://doi.org/10.1186/s40659-024-00490-5","url":null,"abstract":"Galectins are soluble glycan-binding proteins that interact with a wide range of glycoproteins and glycolipids and modulate a broad spectrum of physiological and pathological processes. The expression and subcellular localization of different galectins vary among tissues and cell types and change during processes of tissue repair, fibrosis and cancer where epithelial cells loss differentiation while acquiring migratory mesenchymal phenotypes. The epithelial-mesenchymal transition (EMT) that occurs in the context of these processes can include modifications of glycosylation patterns of glycolipids and glycoproteins affecting their interactions with galectins. Moreover, overexpression of certain galectins has been involved in the development and different outcomes of EMT. This review focuses on the roles and mechanisms of Galectin-1 (Gal-1), Gal-3, Gal-4, Gal-7 and Gal-8, which have been involved in physiologic and pathogenic EMT contexts.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591389","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
Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function. 谷氨酰胺溶解通过调节线粒体功能调节宫腔内粘连的子宫内膜纤维化。
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-01 DOI: 10.1186/s40659-024-00492-3
Pei Chen, Chaoshuang Ye, Yunke Huang, Bingning Xu, Tianyu Wu, Yuanhang Dong, Yang Jin, Li Zhao, Changchang Hu, Jingxia Mao, Ruijin Wu

Background: Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis.

Methods: The activation model of ESCs was constructed by TGF-β1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis.

Results: We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes.

Conclusion: Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.

背景:子宫内膜纤维化是宫腔内粘连(IUA)的一个重要特征,是由子宫内膜基质细胞(ESC)过度分化和活化引起的。谷氨酰胺分解是谷氨酰胺(Gln)的代谢过程,与多种类型的器官纤维化有关。迄今为止,人们对谷氨酰胺溶解是否在子宫内膜纤维化中发挥作用知之甚少:方法:利用 TGF-β1 建立了 ESCs 活化模型,然后进行 RNA 序列分析。实验验证了活化的 ESCs 中谷氨酰胺酶 1(GLS1)在 RNA 和蛋白质水平上的表达变化。收集人类 IUA 样本以验证 GLS1 在子宫内膜纤维化中的表达。将 GLS1 抑制剂和谷氨酰胺剥夺应用于 ESCs 模型,研究谷氨酰胺溶解在 ESCs 活化过程中的生物学功能和机制。建立IUA小鼠模型,探讨谷氨酰胺酵解抑制对子宫内膜纤维化的影响:结果:我们发现,GLS1在活化的ESCs模型和纤维化的子宫内膜中表达明显增加。通过GLS1抑制剂双-2-(5-苯乙酰氨基-1,2,4-噻二唑-2-基)乙基硫醚(BPTES)抑制谷氨酰胺分解或谷氨酰胺剥夺处理,可抑制两种纤维化标志物α-SMA和胶原蛋白I的表达,并抑制ESCs的线粒体功能和mTORC1信号传导。此外,雷帕霉素抑制了 mTORC1 信号通路,从而抑制了 ESCs 的活化。在IUA小鼠模型中,BPTES治疗能明显改善子宫内膜纤维化并改善妊娠结局:结论:谷氨酰胺酵解和谷氨酰胺酵解相关的mTOR信号转导通过调节线粒体功能在激活ESCs和子宫内膜纤维化的发病机制中发挥作用。抑制谷氨酰胺酵解可抑制 ESCs 的活化,这可能是 IUA 的一种新型治疗策略。
{"title":"Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function.","authors":"Pei Chen, Chaoshuang Ye, Yunke Huang, Bingning Xu, Tianyu Wu, Yuanhang Dong, Yang Jin, Li Zhao, Changchang Hu, Jingxia Mao, Ruijin Wu","doi":"10.1186/s40659-024-00492-3","DOIUrl":"10.1186/s40659-024-00492-3","url":null,"abstract":"<p><strong>Background: </strong>Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis.</p><p><strong>Methods: </strong>The activation model of ESCs was constructed by TGF-β1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis.</p><p><strong>Results: </strong>We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes.</p><p><strong>Conclusion: </strong>Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The long-chain flavodoxin FldX1 improves the biodegradation of 4-hydroxyphenylacetate and 3-hydroxyphenylacetate and counteracts the oxidative stress associated to aromatic catabolism in Paraburkholderia xenovorans. 长链黄酮毒素 FldX1 可改善 4-hydroxyphenylacetate 和 3-hydroxyphenylacetate 的生物降解,并抵消 Paraburkholderia xenovorans 中与芳香族分解代谢相关的氧化应激。
IF 6.7 2区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-01 DOI: 10.1186/s40659-024-00491-4
Laura Rodríguez-Castro, Roberto E Durán, Valentina Méndez, Flavia Dorochesi, Daniela Zühlke, Katharina Riedel, Michael Seeger

Background: Bacterial aromatic degradation may cause oxidative stress. The long-chain flavodoxin FldX1 of Paraburkholderia xenovorans LB400 counteracts reactive oxygen species (ROS). The aim of this study was to evaluate the protective role of FldX1 in P. xenovorans LB400 during the degradation of 4-hydroxyphenylacetate (4-HPA) and 3-hydroxyphenylacetate (3-HPA).

Methods: The functionality of FldX1 was evaluated in P. xenovorans p2-fldX1 that overexpresses FldX1. The effects of FldX1 on P. xenovorans were studied measuring growth on hydroxyphenylacetates, degradation of 4-HPA and 3-HPA, and ROS formation. The effects of hydroxyphenylacetates (HPAs) on the proteome (LC-MS/MS) and gene expression (qRT-PCR) were quantified. Bioaugmentation with strain p2-fldX1 of 4-HPA-polluted soil was assessed, measuring aromatic degradation (HPLC), 4-HPA-degrading bacteria, and plasmid stability.

Results: The exposure of P. xenovorans to 4-HPA increased the formation of ROS compared to 3-HPA or glucose. P. xenovorans p2-fldX1 showed an increased growth on 4-HPA and 3-HPA compared to the control strain WT-p2. Strain p2-fldX1 degraded faster 4-HPA and 3-HPA than strain WT-p2. Both WT-p2 and p2-fldX1 cells grown on 4-HPA displayed more changes in the proteome than cells grown on 3-HPA in comparison to glucose-grown cells. Several enzymes involved in ROS detoxification, including AhpC2, AhpF, AhpD3, KatA, Bcp, CpoF1, Prx1 and Prx2, were upregulated by hydroxyphenylacetates. Downregulation of organic hydroperoxide resistance (Ohr) and DpsA proteins was observed. A downregulation of the genes encoding scavenging enzymes (katE and sodB), and gstA and trxB was observed in p2-fldX1 cells, suggesting that FldX1 prevents the antioxidant response. More than 20 membrane proteins, including porins and transporters, showed changes in expression during the growth of both strains on hydroxyphenylacetates. An increased 4-HPA degradation by recombinant strain p2-fldX1 in soil microcosms was observed. In soil, the strain overexpressing the flavodoxin FldX1 showed a lower plasmid loss, compared to WT-p2 strain, suggesting that FldX1 contributes to bacterial fitness. Overall, these results suggest that recombinant strain p2-fldX1 is an attractive bacterium for its application in bioremediation processes of aromatic compounds.

Conclusions: The long-chain flavodoxin FldX1 improved the capability of P. xenovorans to degrade 4-HPA in liquid culture and soil microcosms by protecting cells against the degradation-associated oxidative stress.

背景:细菌的芳香降解可能会导致氧化应激。Paraburkholderia xenovorans LB400 的长链黄酮毒素 FldX1 可抵消活性氧(ROS)。本研究的目的是评估 FldX1 在 Paraburkholderia xenovorans LB400 降解 4-hydroxyphenylacetate (4-HPA) 和 3-hydroxyphenylacetate (3-HPA) 过程中的保护作用:方法:在过表达 FldX1 的 P. xenovorans p2-fldX1 中评估了 FldX1 的功能。方法:在过量表达 FldX1 的 P. xenovorans p2-fldX1 中评估了 FldX1 的功能。研究了 FldX1 对 P. xenovorans 的影响,测量了其在羟基苯乙酸酯上的生长、4-HPA 和 3-HPA 的降解以及 ROS 的形成。还量化了羟基苯乙酸盐(HPAs)对蛋白质组(LC-MS/MS)和基因表达(qRT-PCR)的影响。用菌株 p2-fldX1 对受 4-HPA 污染的土壤进行生物增强评估,测量芳烃降解(HPLC)、4-HPA 降解细菌和质粒稳定性:结果:与 3-HPA 或葡萄糖相比,P. xenovorans 暴露于 4-HPA 会增加 ROS 的形成。与对照菌株 WT-p2 相比,P. xenovorans p2-fldX1 在 4-HPA 和 3-HPA 上的生长速度加快。与 WT-p2 菌株相比,p2-fldX1 菌株降解 4-HPA 和 3-HPA 的速度更快。与生长在葡萄糖中的细胞相比,生长在 4-HPA 上的 WT-p2 和 p2-fldX1 细胞比生长在 3-HPA 上的细胞显示出更多的蛋白质组变化。参与 ROS 解毒的几种酶,包括 AhpC2、AhpF、AhpD3、KatA、Bcp、CpoF1、Prx1 和 Prx2,在羟基苯乙酸盐的作用下上调。观察到有机过氧化氢抗性(Ohr)和 DpsA 蛋白下调。在 p2-fldX1 细胞中观察到编码清除酶(katE 和 sodB)、gstA 和 trxB 的基因下调,这表明 FldX1 阻止了抗氧化反应。在两种菌株在羟基苯乙酸盐上的生长过程中,包括孔蛋白和转运体在内的 20 多种膜蛋白的表达发生了变化。在土壤微生态系统中,重组菌株 p2-fldX1 对 4-HPA 的降解增加。在土壤中,与 WT-p2 菌株相比,过表达黄酮毒素 FldX1 的菌株的质粒损失较少,这表明 FldX1 对细菌的适应性有贡献。总之,这些结果表明,重组菌株 p2-fldX1 是一种有吸引力的细菌,可用于芳香族化合物的生物修复过程:结论:长链黄酮毒素 FldX1 通过保护细胞免受与降解相关的氧化应激,提高了 P. xenovorans 在液体培养和土壤微生态系统中降解 4-HPA 的能力。
{"title":"The long-chain flavodoxin FldX1 improves the biodegradation of 4-hydroxyphenylacetate and 3-hydroxyphenylacetate and counteracts the oxidative stress associated to aromatic catabolism in Paraburkholderia xenovorans.","authors":"Laura Rodríguez-Castro, Roberto E Durán, Valentina Méndez, Flavia Dorochesi, Daniela Zühlke, Katharina Riedel, Michael Seeger","doi":"10.1186/s40659-024-00491-4","DOIUrl":"10.1186/s40659-024-00491-4","url":null,"abstract":"<p><strong>Background: </strong>Bacterial aromatic degradation may cause oxidative stress. The long-chain flavodoxin FldX1 of Paraburkholderia xenovorans LB400 counteracts reactive oxygen species (ROS). The aim of this study was to evaluate the protective role of FldX1 in P. xenovorans LB400 during the degradation of 4-hydroxyphenylacetate (4-HPA) and 3-hydroxyphenylacetate (3-HPA).</p><p><strong>Methods: </strong>The functionality of FldX1 was evaluated in P. xenovorans p2-fldX1 that overexpresses FldX1. The effects of FldX1 on P. xenovorans were studied measuring growth on hydroxyphenylacetates, degradation of 4-HPA and 3-HPA, and ROS formation. The effects of hydroxyphenylacetates (HPAs) on the proteome (LC-MS/MS) and gene expression (qRT-PCR) were quantified. Bioaugmentation with strain p2-fldX1 of 4-HPA-polluted soil was assessed, measuring aromatic degradation (HPLC), 4-HPA-degrading bacteria, and plasmid stability.</p><p><strong>Results: </strong>The exposure of P. xenovorans to 4-HPA increased the formation of ROS compared to 3-HPA or glucose. P. xenovorans p2-fldX1 showed an increased growth on 4-HPA and 3-HPA compared to the control strain WT-p2. Strain p2-fldX1 degraded faster 4-HPA and 3-HPA than strain WT-p2. Both WT-p2 and p2-fldX1 cells grown on 4-HPA displayed more changes in the proteome than cells grown on 3-HPA in comparison to glucose-grown cells. Several enzymes involved in ROS detoxification, including AhpC2, AhpF, AhpD3, KatA, Bcp, CpoF1, Prx1 and Prx2, were upregulated by hydroxyphenylacetates. Downregulation of organic hydroperoxide resistance (Ohr) and DpsA proteins was observed. A downregulation of the genes encoding scavenging enzymes (katE and sodB), and gstA and trxB was observed in p2-fldX1 cells, suggesting that FldX1 prevents the antioxidant response. More than 20 membrane proteins, including porins and transporters, showed changes in expression during the growth of both strains on hydroxyphenylacetates. An increased 4-HPA degradation by recombinant strain p2-fldX1 in soil microcosms was observed. In soil, the strain overexpressing the flavodoxin FldX1 showed a lower plasmid loss, compared to WT-p2 strain, suggesting that FldX1 contributes to bacterial fitness. Overall, these results suggest that recombinant strain p2-fldX1 is an attractive bacterium for its application in bioremediation processes of aromatic compounds.</p><p><strong>Conclusions: </strong>The long-chain flavodoxin FldX1 improved the capability of P. xenovorans to degrade 4-HPA in liquid culture and soil microcosms by protecting cells against the degradation-associated oxidative stress.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Biological Research
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