首页 > 最新文献

Peptides最新文献

英文 中文
Host defense peptides in crocodilians – A comprehensive review 鳄鱼的宿主防御肽--全面综述。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.peptides.2024.171312
Trinidad de los Ángeles Cordero Gil , María Soledad Moleón , Belkis Ester Marelli , Pablo Ariel Siroski
Amphibians and reptiles, like all animals, are prone to periodic infections. However, crocodilians stand out for their remarkable ability to remain generally healthy and infection-free despite frequent exposure to a wide variety of microorganisms in their habitats and often sustaining significant injuries. These animals have evolved highly active immune mechanisms that provide rapid and effective defense. This is evidenced by the superior hemolytic capacity of their plasma compared to that of other organisms. To date, several host defense peptides (HDPs) have been identified in crocodilians, including cathelicidins, beta-defensins, hepcidins, leucrocins, hemocidins, and omwaprins. These peptides exhibit potent and broad-spectrum antimicrobial, antibiofilm, antifungal, and anticancer activities. Due to the relatively low but diverse evolutionary rate of crocodilians, the HDPs found in this species offer valuable insights into proteins and mechanisms of action that are highly conserved across many animals related to immune defense. The potential applications of HDPs in modern medicine represent a promising strategy for developing new therapeutic agents. Their novelty and the vast variability with which peptide sequences can be designed and modified expand the field of application for HDPs almost infinitely. This review addresses the urgent need for innovative and more effective drugs to combat the rise of antimicrobialresistant infections and evaluates the potential of crocodilian HDPs. It presents recent advances in the identification of crocodilian HDPs, particularly antimicrobial peptides (AMPs), including previously underexplored topics such as the sequential and structural conformation of different peptide types in crocodilians and the use of bioinformatics tools to enhance native peptides
两栖动物和爬行动物与所有动物一样,容易受到周期性感染。然而,鳄鱼的与众不同之处在于,尽管它们经常接触栖息地中的各种微生物,而且经常受到严重伤害,但它们仍能保持总体健康和不受感染。这些动物进化出了高度活跃的免疫机制,能够提供快速有效的防御。与其他生物相比,它们的血浆具有更强的溶血能力,这就证明了这一点。迄今为止,已在鳄鱼体内发现了几种宿主防御肽(HDPs),包括cathelicidins、beta-defensins、hepcidins、leucrocins、hemocidins和omwaprins。这些肽具有强效、广谱的抗菌、抗生物膜、抗真菌和抗癌活性。由于鳄鱼的进化速度相对较低,但进化方式多种多样,因此在该物种中发现的 HDPs 为了解与免疫防御有关的许多动物高度保守的蛋白质和作用机制提供了宝贵的信息。HDPs 在现代医学中的潜在应用为开发新的治疗药物提供了一种前景广阔的策略。它们的新颖性以及肽序列设计和修饰的巨大可变性几乎无限地扩展了 HDPs 的应用领域。本综述探讨了对创新和更有效药物的迫切需求,以应对抗生素耐药性感染的增加,并评估了鳄鱼 HDPs 的潜力。它介绍了鳄鱼 HDPs,特别是抗菌肽(AMPs)鉴定的最新进展,包括以前未充分探索的主题,如鳄鱼中不同类型肽的序列和结构构象,以及使用生物信息学工具来增强本地肽。
{"title":"Host defense peptides in crocodilians – A comprehensive review","authors":"Trinidad de los Ángeles Cordero Gil ,&nbsp;María Soledad Moleón ,&nbsp;Belkis Ester Marelli ,&nbsp;Pablo Ariel Siroski","doi":"10.1016/j.peptides.2024.171312","DOIUrl":"10.1016/j.peptides.2024.171312","url":null,"abstract":"<div><div>Amphibians and reptiles, like all animals, are prone to periodic infections. However, crocodilians stand out for their remarkable ability to remain generally healthy and infection-free despite frequent exposure to a wide variety of microorganisms in their habitats and often sustaining significant injuries. These animals have evolved highly active immune mechanisms that provide rapid and effective defense. This is evidenced by the superior hemolytic capacity of their plasma compared to that of other organisms. To date, several host defense peptides (HDPs) have been identified in crocodilians, including cathelicidins, beta-defensins, hepcidins, leucrocins, hemocidins, and omwaprins. These peptides exhibit potent and broad-spectrum antimicrobial, antibiofilm, antifungal, and anticancer activities. Due to the relatively low but diverse evolutionary rate of crocodilians, the HDPs found in this species offer valuable insights into proteins and mechanisms of action that are highly conserved across many animals related to immune defense. The potential applications of HDPs in modern medicine represent a promising strategy for developing new therapeutic agents. Their novelty and the vast variability with which peptide sequences can be designed and modified expand the field of application for HDPs almost infinitely. This review addresses the urgent need for innovative and more effective drugs to combat the rise of antimicrobialresistant infections and evaluates the potential of crocodilian HDPs. It presents recent advances in the identification of crocodilian HDPs, particularly antimicrobial peptides (AMPs), including previously underexplored topics such as the sequential and structural conformation of different peptide types in crocodilians and the use of bioinformatics tools to enhance native peptides</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171312"},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cm-p5, a molluscan-derived antifungal peptide exerts its activity by a membrane surface covering in a non-penetrating mode 源于软体动物的抗真菌肽 Cm-p5 通过膜表面覆盖以非穿透方式发挥活性
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-26 DOI: 10.1016/j.peptides.2024.171313
M. Gonzalez-Garcia , B. Bertrand , EM Martell-Huguet , JF Espinosa-Romero , RF Vázquez , F. Morales –Vicente , F. Rosenau , LH Standker , OL Franco , AJ Otero-Gonzalez , C Muñoz-Garay
Amidst the health crisis caused by the rise of multi-resistant pathogenic microorganisms, Antimicrobial Peptides (AMPs) have emerged as a potential alternative to traditional antibiotics. In this sense, Cm-p5 is an AMP with fungistatic activity against the yeast Candida albicans. Its antimicrobial activity and selectivity have been well characterized; however, the mechanism of action is still unknown. This study used biophysical approaches to gain insight into how this peptide exerts its activity. Stability and fluidity of lipid membrane were explored by liposome leakage and Laurdan generalized polarization (GP) respectively, suggesting that Cm-p5 does not perturb lipid membranes even at very high concentrations (≥100 µm.L−1). Likewise, no depolarizing action was observed using 3,3′-propil-2,2′-thyodicarbocianine, a potential membrane fluorescent reporter, with C. albicans cells or the corresponding liposome models. Changes in liposome size were analyzed by Dynamic Light Scattering (DLS) data, indicating that Cm-p5 covers the vesicular surface slightly increasing liposome hydrodynamic size, without liposome rupture. These results were further corroborated with Langmuir monolayer isotherms, where no significant changes in lateral pressure or area per lipid were detected, indicating little or no insertion. Finally, data obtained from molecular dynamics simulations aligned with in vitro observations, whereby Cm-p5 slightly interacted with the fungal membrane model surface without causing significant perturbation. These results suggest Cm-p5 is not a pore-forming anti-fungal peptide and that other mechanisms of action on the membrane as some limitation of fungal nutrition or receptor-dependent transduction for depressing growth development should be explored.
多重耐药性病原微生物的增加引发了健康危机,在此背景下,抗菌肽(AMP)作为传统抗生素的潜在替代品应运而生。从这个意义上说,Cm-p5 是一种对白色念珠菌酵母具有杀真菌活性的 AMP。它的抗菌活性和选择性已经得到了很好的表征,但其作用机制仍然未知。本研究采用生物物理方法来深入了解这种多肽是如何发挥其活性的。通过脂质体渗漏和劳尔丹泛化极化(GP)分别探讨了脂膜的稳定性和流动性,结果表明即使在非常高的浓度(≥100 µm.L-1)下,Cm-p5也不会扰乱脂膜。同样,在白僵菌细胞或相应的脂质体模型中使用 3,3′-丙基-2,2′-硫代二碳滇碱(一种潜在的膜荧光报告物)也没有观察到去极化作用。通过动态光散射(DLS)数据分析了脂质体大小的变化,结果表明 Cm-p5 覆盖在囊泡表面会略微增加脂质体的流体力学大小,但不会导致脂质体破裂。朗缪尔单层等温线进一步证实了这些结果,在这些等温线上检测到横向压力或每个脂质的面积没有显著变化,表明几乎没有插入。最后,分子动力学模拟获得的数据与体外观察结果一致,Cm-p5 与真菌膜模型表面有轻微的相互作用,没有造成明显的扰动。这些结果表明,Cm-p5 并不是一种能形成孔隙的抗真菌肽,因此应探索其对真菌膜的其他作用机制,如限制真菌营养或受体依赖性传导以抑制生长发育。
{"title":"Cm-p5, a molluscan-derived antifungal peptide exerts its activity by a membrane surface covering in a non-penetrating mode","authors":"M. Gonzalez-Garcia ,&nbsp;B. Bertrand ,&nbsp;EM Martell-Huguet ,&nbsp;JF Espinosa-Romero ,&nbsp;RF Vázquez ,&nbsp;F. Morales –Vicente ,&nbsp;F. Rosenau ,&nbsp;LH Standker ,&nbsp;OL Franco ,&nbsp;AJ Otero-Gonzalez ,&nbsp;C Muñoz-Garay","doi":"10.1016/j.peptides.2024.171313","DOIUrl":"10.1016/j.peptides.2024.171313","url":null,"abstract":"<div><div>Amidst the health crisis caused by the rise of multi-resistant pathogenic microorganisms, Antimicrobial Peptides (AMPs) have emerged as a potential alternative to traditional antibiotics. In this sense, Cm-p5 is an AMP with fungistatic activity against the yeast <em>Candida albicans</em>. Its antimicrobial activity and selectivity have been well characterized; however, the mechanism of action is still unknown. This study used biophysical approaches to gain insight into how this peptide exerts its activity. Stability and fluidity of lipid membrane were explored by liposome leakage and Laurdan generalized polarization (GP) respectively, suggesting that Cm-p5 does not perturb lipid membranes even at very high concentrations (≥100 µm.L<sup>−1</sup>). Likewise, no depolarizing action was observed using 3,3′-propil-2,2′-thyodicarbocianine, a potential membrane fluorescent reporter, with <em>C. albicans</em> cells or the corresponding liposome models. Changes in liposome size were analyzed by Dynamic Light Scattering (DLS) data, indicating that Cm-p5 covers the vesicular surface slightly increasing liposome hydrodynamic size, without liposome rupture. These results were further corroborated with Langmuir monolayer isotherms, where no significant changes in lateral pressure or area per lipid were detected, indicating little or no insertion. Finally, data obtained from molecular dynamics simulations aligned with <em>in vitro</em> observations, whereby Cm-p5 slightly interacted with the fungal membrane model surface without causing significant perturbation. These results suggest Cm-p5 is not a pore-forming anti-fungal peptide and that other mechanisms of action on the membrane as some limitation of fungal nutrition or receptor-dependent transduction for depressing growth development should be explored.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171313"},"PeriodicalIF":2.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Suppression of B-type natriuretic peptide gene expression in cardiomyocytes under anoxic conditions 缺氧条件下抑制心肌细胞中 B 型钠尿肽基因的表达
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-25 DOI: 10.1016/j.peptides.2024.171316
Rei Yasutake, Tomohisa Nagoshi, Akira Yoshii, Hirotake Takahashi, Yuhei Oi, Haruka Kimura, Yusuke Kashiwagi, Toshikazu D. Tanaka, Yoshiro Tanaka, Michihiro Yoshimura
Several cell biology studies have focused on the effects of hypoxic environments on cardiomyocytes. However, the effect of anoxic conditions on cardiomyocytes remains largely unexplored. In the present study, we investigated the direct effects of anoxia on B-type natriuretic peptide (BNP) gene expression in cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) were exposed to anoxia using an airtight chamber saturated with 95 % N2/5 % CO2. BNP mRNA levels in NRCM were substantially reduced after more than 8 h of anoxia exposure, whereas after reoxygenation, BNP gene expression levels recovered in a time-dependent manner and significantly increased after 24 h of reoxygenation. BNP mRNA levels suppressed under anoxic conditions were significantly increased by aldosterone-induced activation of sodium-proton exchanger 1 (NHE1), which was canceled by an NHE1 inhibitor, suggesting that anoxia reduces BNP gene expression, at least in part, in an NHE1-dependent manner. In summary, we found that BNP gene expression in cardiomyocytes decreases under anoxic conditions, in contrast to previous research findings that BNP expression increases under hypoxic conditions. These findings reveal a new insight that, within a single heart tissue in various cardiovascular diseases, such as myocardial infarction, the biological responses of cardiomyocytes are fundamentally different in regions of anoxia and hypoxia.
一些细胞生物学研究主要关注缺氧环境对心肌细胞的影响。然而,缺氧条件对心肌细胞的影响在很大程度上仍未得到探讨。在本研究中,我们研究了缺氧对心肌细胞中 B 型钠尿肽(BNP)基因表达的直接影响。使用 95% N2/5% CO2 饱和的密闭室将新生大鼠心肌细胞(NRCMs)暴露于缺氧状态。缺氧超过 8 小时后,NRCM 中的 BNP mRNA 水平大幅降低,而复氧后,BNP 基因表达水平以时间依赖性方式恢复,并在复氧 24 小时后显著增加。缺氧条件下被抑制的 BNP mRNA 水平在醛固酮诱导的钠-质子交换子 1(NHE1)激活后显著升高,而 NHE1 抑制剂可消除这种激活,这表明缺氧至少部分以 NHE1 依赖性的方式降低了 BNP 基因的表达。总之,我们发现缺氧条件下心肌细胞中 BNP 基因表达减少,这与之前研究发现缺氧条件下 BNP 表达增加形成了鲜明对比。这些发现揭示了一个新的观点,即在各种心血管疾病(如心肌梗塞)中,在单个心脏组织内,心肌细胞在缺氧和缺氧区域的生物反应是根本不同的。
{"title":"Suppression of B-type natriuretic peptide gene expression in cardiomyocytes under anoxic conditions","authors":"Rei Yasutake,&nbsp;Tomohisa Nagoshi,&nbsp;Akira Yoshii,&nbsp;Hirotake Takahashi,&nbsp;Yuhei Oi,&nbsp;Haruka Kimura,&nbsp;Yusuke Kashiwagi,&nbsp;Toshikazu D. Tanaka,&nbsp;Yoshiro Tanaka,&nbsp;Michihiro Yoshimura","doi":"10.1016/j.peptides.2024.171316","DOIUrl":"10.1016/j.peptides.2024.171316","url":null,"abstract":"<div><div>Several cell biology studies have focused on the effects of hypoxic environments on cardiomyocytes. However, the effect of anoxic conditions on cardiomyocytes remains largely unexplored. In the present study, we investigated the direct effects of anoxia on B-type natriuretic peptide (BNP) gene expression in cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) were exposed to anoxia using an airtight chamber saturated with 95 % N<sub>2</sub>/5 % CO<sub>2</sub>. BNP mRNA levels in NRCM were substantially reduced after more than 8 h of anoxia exposure, whereas after reoxygenation, BNP gene expression levels recovered in a time-dependent manner and significantly increased after 24 h of reoxygenation. BNP mRNA levels suppressed under anoxic conditions were significantly increased by aldosterone-induced activation of sodium-proton exchanger 1 (NHE1), which was canceled by an NHE1 inhibitor, suggesting that anoxia reduces BNP gene expression, at least in part, in an NHE1-dependent manner. In summary, we found that BNP gene expression in cardiomyocytes decreases under anoxic conditions, in contrast to previous research findings that BNP expression increases under hypoxic conditions. These findings reveal a new insight that, within a single heart tissue in various cardiovascular diseases, such as myocardial infarction, the biological responses of cardiomyocytes are fundamentally different in regions of anoxia and hypoxia.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171316"},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modulation of amylin and calcitonin receptor activation by hybrid peptides 混合肽对淀粉样蛋白和降钙素受体活化的调节。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.peptides.2024.171314
Sangmin Lee
Calcitonin peptide hormone controls calcium homeostasis by activating the calcitonin receptor. When the calcitonin receptor forms a complex with an accessory protein, the complex functions as the receptors for another peptide hormone amylin. The amylin receptors are the drug target for diabetes and obesity treatment. Since human amylin can produce aggregates, rat amylin that does not form aggregates has been commonly used for research. Interestingly, calcitonin originated from salmons was reported to interact with human amylin receptors with higher affinity/potency than endogenous rat amylin. Here, the peptide hybrid was made of a rat amylin N-terminal fragment and a salmon calcitonin C-terminal fragment. This novel hybrid peptide showed higher potency for human amylin receptor 1/2 activation by 6- to 8-fold than endogenous rat amylin. To further examine the role of the peptide C-terminal fragment in receptor activation, another hybrid peptide was made where salmon calcitonin N-terminal 21 amino acids were fused with rat amylin C-terminal 11 amino acids. The rat amylin C-terminal fragment was previously reported to have relatively low affinity for calcitonin receptor extracellular domain. As expected, this calcitonin-amylin hybrid peptide decreased the potency for calcitonin receptor activation by 3-fold compared to salmon calcitonin. The hybrid strategy used in this study significantly changed the peptide potency for amylin and calcitonin receptor activation. These results provide insight into the role of peptide C-terminal fragments in modulating amylin and calcitonin receptor activation.
降钙素肽激素通过激活降钙素受体来控制钙平衡。当降钙素受体与附属蛋白形成复合物时,该复合物就成为另一种肽类激素淀粉样蛋白的受体。淀粉素受体是治疗糖尿病和肥胖症的药物靶点。由于人类淀粉样蛋白会产生聚集体,因此研究中通常使用不会形成聚集体的大鼠淀粉样蛋白。有趣的是,有报道称源自鲑鱼的降钙素与人淀粉样蛋白受体相互作用,其亲和力/效力高于内源性大鼠淀粉样蛋白。在这里,大鼠淀粉样蛋白 N 端片段和鲑鱼降钙素 C 端片段被制成了多肽杂交肽。与内源性大鼠淀粉样蛋白相比,这种新型杂交肽对人淀粉样蛋白受体1/2的激活效力高出6至8倍。为了进一步研究肽 C 端片段在受体激活中的作用,我们又制作了另一种杂交肽,将鲑降钙素 N 端 21 个氨基酸与大鼠淀粉样蛋白 C 端 11 个氨基酸融合。之前有报道称,大鼠淀粉样蛋白 C 端片段与降钙素受体胞外结构域的亲和力相对较低。不出所料,与鲑鱼降钙素相比,这种降钙素-淀粉样蛋白杂交肽激活降钙素受体的效力降低了 3 倍。本研究采用的杂交策略显著改变了肽激活淀粉样蛋白和降钙素受体的效力。这些结果让我们了解了多肽 C 端片段在调节淀粉样蛋白和降钙素受体活化过程中的作用。
{"title":"Modulation of amylin and calcitonin receptor activation by hybrid peptides","authors":"Sangmin Lee","doi":"10.1016/j.peptides.2024.171314","DOIUrl":"10.1016/j.peptides.2024.171314","url":null,"abstract":"<div><div>Calcitonin peptide hormone controls calcium homeostasis by activating the calcitonin receptor. When the calcitonin receptor forms a complex with an accessory protein, the complex functions as the receptors for another peptide hormone amylin. The amylin receptors are the drug target for diabetes and obesity treatment. Since human amylin can produce aggregates, rat amylin that does not form aggregates has been commonly used for research. Interestingly, calcitonin originated from salmons was reported to interact with human amylin receptors with higher affinity/potency than endogenous rat amylin. Here, the peptide hybrid was made of a rat amylin N-terminal fragment and a salmon calcitonin C-terminal fragment. This novel hybrid peptide showed higher potency for human amylin receptor 1/2 activation by 6- to 8-fold than endogenous rat amylin. To further examine the role of the peptide C-terminal fragment in receptor activation, another hybrid peptide was made where salmon calcitonin N-terminal 21 amino acids were fused with rat amylin C-terminal 11 amino acids. The rat amylin C-terminal fragment was previously reported to have relatively low affinity for calcitonin receptor extracellular domain. As expected, this calcitonin-amylin hybrid peptide decreased the potency for calcitonin receptor activation by 3-fold compared to salmon calcitonin. The hybrid strategy used in this study significantly changed the peptide potency for amylin and calcitonin receptor activation. These results provide insight into the role of peptide C-terminal fragments in modulating amylin and calcitonin receptor activation.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171314"},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nesfatin-1 expressed in human endometrial stromal cell line (THESC) stimulates decidualization through FAK/PI3K/AKT signaling pathway 在人子宫内膜基质细胞系(THESC)中表达的Nesfatin-1通过FAK/PI3K/AKT信号通路刺激蜕膜化。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.peptides.2024.171315
Jinah Ha, Hyunwon Yang
This study aimed to investigate the expression and functional role of nesfatin-1, a peptide hormone traditionally associated with appetite regulation, in the human endometrium. Specifically, we examined its presence and regulatory potential in the human endometrial stromal cell line, THESC cells, focusing on the process of endometrial decidualization, which is critical for implantation and pregnancy maintenance. We found that nesfatin-1 and its binding sites were expressed in THESC cells. Furthermore, nesfatin-1 protein expression decreased after treatment with 17β-estradiol but increased upon exposure to progesterone, indicating an influence of sexsteroid hormones on nesfatin-1 expression. Notably, administration of nesfatin-1 protein to THESC cells resulted in significant upregulation of genes associated with decidualization, such as insulin-like growth factor binding protein 1 (IGFBP1) and prolactin. In addition, our research showed that nesfatin-1 promotes decidualization through the activation of the FAK/PI3K/AKT signaling pathway. These findings underscore the central role of nesfatin-1 in endometrial decidualization, and suggest its potential utility in the development of new treatments to improve fertility and pregnancy outcomes.
本研究旨在探讨传统上与食欲调节有关的肽类激素内司芬-1在人类子宫内膜中的表达和功能作用。具体来说,我们研究了它在人类子宫内膜基质细胞系THESC细胞中的存在和调控潜力,重点关注子宫内膜蜕膜化过程,该过程对着床和维持妊娠至关重要。我们发现,nesfatin-1及其结合位点在THESC细胞中表达。此外,17β-雌二醇处理后,nesfatin-1蛋白表达量减少,但黄体酮处理后,nesfatin-1蛋白表达量增加,这表明类性激素对nesfatin-1的表达有影响。值得注意的是,给THESC细胞注射nesfatin-1蛋白会导致与蜕膜化相关的基因(如胰岛素样生长因子结合蛋白1(IGFBP1)和催乳素)显著上调。此外,我们的研究还表明,nesfatin-1能通过激活FAK/PI3K/AKT信号通路促进蜕膜化。这些发现强调了内司蛋白-1在子宫内膜蜕膜化中的核心作用,并表明它在开发新的治疗方法以改善生育能力和妊娠结局方面具有潜在的用途。
{"title":"Nesfatin-1 expressed in human endometrial stromal cell line (THESC) stimulates decidualization through FAK/PI3K/AKT signaling pathway","authors":"Jinah Ha,&nbsp;Hyunwon Yang","doi":"10.1016/j.peptides.2024.171315","DOIUrl":"10.1016/j.peptides.2024.171315","url":null,"abstract":"<div><div>This study aimed to investigate the expression and functional role of nesfatin-1, a peptide hormone traditionally associated with appetite regulation, in the human endometrium. Specifically, we examined its presence and regulatory potential in the human endometrial stromal cell line, THESC cells, focusing on the process of endometrial decidualization, which is critical for implantation and pregnancy maintenance. We found that nesfatin-1 and its binding sites were expressed in THESC cells. Furthermore, nesfatin-1 protein expression decreased after treatment with 17β-estradiol but increased upon exposure to progesterone, indicating an influence of sexsteroid hormones on nesfatin-1 expression. Notably, administration of nesfatin-1 protein to THESC cells resulted in significant upregulation of genes associated with decidualization, such as insulin-like growth factor binding protein 1 (IGFBP1) and prolactin. In addition, our research showed that nesfatin-1 promotes decidualization through the activation of the FAK/PI3K/AKT signaling pathway. These findings underscore the central role of nesfatin-1 in endometrial decidualization, and suggest its potential utility in the development of new treatments to improve fertility and pregnancy outcomes.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171315"},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Membrane alteration, anti-virulence properties and metabolomic perturbation of a chionodracine-derived antimicrobial peptide, KHS-Cnd, on two bacteria models 一种源自chionodracine的抗菌肽KHS-Cnd对两种细菌模型的膜改变、抗病毒特性和代谢组扰动。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.peptides.2024.171311
Esther Imperlini , Federica Massaro , Angelica Grifoni , Francesco Maiurano , Anna Rita Taddei , Stefano Borocci , Francesco Buonocore , Fernando Porcelli
Antarctic fishes, living in an extreme environment and normally exposed to pathogens, are a promising source of antimicrobial peptides (AMPs). These are emerging as next-generation drugs due to their activity against multidrug resistant (MDR) bacteria. To infect hosts, beyond intrinsic/acquired resistance, MDR species also use virulence factors such as protease secretion. Hence, AMPs targeting virulence factors could represent a novel strategy to counteract the antimicrobial resistance (AMR). In this paper, we focused on a mutant peptide, named KHS-Cnd, that was obtained from the scaffold of the chionodracine (Cnd), a natural peptide identified in the icefish Chionodraco hamatus. We studied different effects caused by the peptide interaction with the cell membrane of two model bacteria, E. coli and B. cereus. First, we investigated its membranolytic activity revealing that the peptide action is more evident on E. coli, with a 69 % uptake of the used dye at 3 μM, whereas for B. cereus we found only a 65 % uptake at 6 μM. Successively, we determined the impact of this lysis on total protein concentration in the medium and an increase was estimated for both bacteria (84 % after 1 h for E. coli and 90 % for B. cereus, respectively). Moreover, we evaluated the changes in the proteolytic activity of the supernatant, that is an important aspect of bacterial resistance, showing that there was a significant reduction for both bacteria, although at higher level in the case of E. coli. The membranolytic activity was evidenced also morphologically with TEM analysis and a different alteration was evidenced for the two bacteria. Moreover, NMR metabolomics analysis showed that peptide induces changes in E. coli and B. cereus extracellular metabolites especially at the higher tested concentrations: this metabolic variation could be used as a fingerprinting of the peptide action on bacteria physiology due to its interaction with cell wall. Finally, we determined the KHS-Cnd cytotoxicity on human primary cell lines to verify its selectivity toward bacterial cell membranes and we found low toxicity until a concentration of 5 μM. Considering that the peptide exerts both membranolytic and anti-virulence activity on E. coli at 1.5 μM, we confirmed the interesting potential of this AMP as a new drug to counteract AMR.
南极鱼类生活在极端环境中,通常会接触到病原体,是抗菌肽(AMPs)的重要来源。由于其对耐多药(MDR)细菌的活性,这些抗菌肽正在成为下一代药物。为了感染宿主,除了内在/获得性抗药性外,MDR 菌种还利用蛋白酶分泌等毒力因子。因此,以毒力因子为目标的 AMPs 可能是对抗抗菌药耐药性(AMR)的一种新策略。在本文中,我们重点研究了一种名为 KHS-Cnd 的突变肽,这种肽是从冰鱼 Chionodraco hamatus 发现的天然肽 chionodracine (Cnd) 的支架上获得的。我们研究了该肽与两种模式细菌(大肠杆菌和蜡样芽孢杆菌)的细胞膜相互作用所产生的不同效果。首先,我们研究了肽的膜溶解活性,发现肽对大肠杆菌的作用更为明显,在 3 μM 的浓度下,所用染料的吸收率为 69%,而在 6 μM 的浓度下,对蜡样芽孢杆菌的吸收率仅为 65%。随后,我们测定了这种裂解对培养基中总蛋白质浓度的影响,结果发现这两种细菌的蛋白质浓度都有所增加(1 小时后大肠杆菌和蜡样芽孢杆菌的蛋白质浓度分别增加了 84% 和 90%)。此外,我们还评估了上清液蛋白水解活性的变化(这是细菌抵抗力的一个重要方面),结果显示两种细菌的蛋白水解活性都显著降低,但大肠杆菌的蛋白水解活性更高。膜溶解活性还通过 TEM 分析得到了形态学上的证明,而且两种细菌都发生了不同的变化。此外,核磁共振代谢组学分析表明,肽会引起大肠杆菌和蜡样芽孢杆菌胞外代谢物的变化,尤其是在测试浓度较高的情况下:这种代谢变化可用作肽与细胞壁相互作用对细菌生理作用的指纹图谱。最后,我们测定了 KHS-Cnd 对人类原代细胞系的细胞毒性,以验证其对细菌细胞膜的选择性。考虑到该肽在 1.5 μM 浓度下对大肠杆菌具有溶膜和抗病毒活性,我们证实了这种 AMP 作为抗 AMR 新药的有趣潜力。
{"title":"Membrane alteration, anti-virulence properties and metabolomic perturbation of a chionodracine-derived antimicrobial peptide, KHS-Cnd, on two bacteria models","authors":"Esther Imperlini ,&nbsp;Federica Massaro ,&nbsp;Angelica Grifoni ,&nbsp;Francesco Maiurano ,&nbsp;Anna Rita Taddei ,&nbsp;Stefano Borocci ,&nbsp;Francesco Buonocore ,&nbsp;Fernando Porcelli","doi":"10.1016/j.peptides.2024.171311","DOIUrl":"10.1016/j.peptides.2024.171311","url":null,"abstract":"<div><div>Antarctic fishes, living in an extreme environment and normally exposed to pathogens, are a promising source of antimicrobial peptides (AMPs). These are emerging as next-generation drugs due to their activity against multidrug resistant (MDR) bacteria. To infect hosts, beyond intrinsic/acquired resistance, MDR species also use virulence factors such as protease secretion. Hence, AMPs targeting virulence factors could represent a novel strategy to counteract the antimicrobial resistance (AMR). In this paper, we focused on a mutant peptide, named KHS-Cnd, that was obtained from the scaffold of the chionodracine (Cnd), a natural peptide identified in the icefish <em>Chionodraco hamatus</em>. We studied different effects caused by the peptide interaction with the cell membrane of two model bacteria, <em>E. coli</em> and <em>B. cereus</em>. First, we investigated its membranolytic activity revealing that the peptide action is more evident on <em>E. coli</em>, with a 69 % uptake of the used dye at 3 μM, whereas for <em>B. cereus</em> we found only a 65 % uptake at 6 μM. Successively, we determined the impact of this lysis on total protein concentration in the medium and an increase was estimated for both bacteria (84 % after 1 h for <em>E. coli</em> and 90 % for <em>B. cereus</em>, respectively). Moreover, we evaluated the changes in the proteolytic activity of the supernatant, that is an important aspect of bacterial resistance, showing that there was a significant reduction for both bacteria, although at higher level in the case of <em>E. coli</em>. The membranolytic activity was evidenced also morphologically with TEM analysis and a different alteration was evidenced for the two bacteria. Moreover, NMR metabolomics analysis showed that peptide induces changes in <em>E. coli</em> and <em>B. cereus</em> extracellular metabolites especially at the higher tested concentrations: this metabolic variation could be used as a fingerprinting of the peptide action on bacteria physiology due to its interaction with cell wall. Finally, we determined the KHS-Cnd cytotoxicity on human primary cell lines to verify its selectivity toward bacterial cell membranes and we found low toxicity until a concentration of 5 μM. Considering that the peptide exerts both membranolytic and anti-virulence activity on <em>E. coli</em> at 1.5 μM, we confirmed the interesting potential of this AMP as a new drug to counteract AMR.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171311"},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure and function of neurohypophysial hormones 神经生理激素的结构和功能。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-10 DOI: 10.1016/j.peptides.2024.171300
Yasumasa Iwasaki , Yoko Yamaguchi , Mitsuru Nishiyama
Vasopressin (VP) and oxytocin (OXT) are neuropeptides that are synthesized in the hypothalamus and stored in/secreted from the neurohypophysis. Although VP and OXT were initially characterized as osmoregulatory and reproductive hormones, respectively, these peptides exert versatile actions not only in peripheral organs but also in the central nervous system via multiple G protein-coupled receptors. Orthologous peptides and receptors have been identified in various animal phyla, reflecting an ancient origin of this hormone family. The aim of this review is to provide basic information on this hormone family and to propose matters to be addressed in future studies. In the earlier sections of this review, we summarize the historical aspect of VP/OXT research as well as the basic features of hormonal peptides and corresponding receptors. The latter sections describe VP/OXT family peptides and their receptors in nonmammalian species, including invertebrates, to introduce the evolutionary aspect of this hormone family. By integrating knowledge from both general and comparative endocrinology perspectives, we highlight current and future research trends about the VP/OXT system.
血管加压素(VP)和催产素(OXT)是一种神经肽,在下丘脑中合成,并储存在神经丘脑中/从神经丘脑中分泌。虽然 VP 和 OXT 最初分别被定性为渗透调节激素和生殖激素,但这些肽不仅在外周器官中发挥多功能作用,而且还通过多种 G 蛋白偶联受体在中枢神经系统中发挥多功能作用。在不同的动物门类中都发现了同源的肽和受体,这反映了该激素家族的古老起源。本综述旨在提供有关该激素家族的基本信息,并提出未来研究中需要解决的问题。在综述的前几部分,我们总结了 VP/OXT 研究的历史,以及激素肽和相应受体的基本特征。后面的章节介绍了非哺乳动物(包括无脊椎动物)中的 VP/OXT 家族肽及其受体,从而介绍了该激素家族的进化情况。通过整合一般内分泌学和比较内分泌学的知识,我们强调了有关 VP/OXT 系统的当前和未来研究趋势。
{"title":"Structure and function of neurohypophysial hormones","authors":"Yasumasa Iwasaki ,&nbsp;Yoko Yamaguchi ,&nbsp;Mitsuru Nishiyama","doi":"10.1016/j.peptides.2024.171300","DOIUrl":"10.1016/j.peptides.2024.171300","url":null,"abstract":"<div><div>Vasopressin (VP) and oxytocin (OXT) are neuropeptides that are synthesized in the hypothalamus and stored in/secreted from the neurohypophysis. Although VP and OXT were initially characterized as osmoregulatory and reproductive hormones, respectively, these peptides exert versatile actions not only in peripheral organs but also in the central nervous system via multiple G protein-coupled receptors. Orthologous peptides and receptors have been identified in various animal phyla, reflecting an ancient origin of this hormone family. The aim of this review is to provide basic information on this hormone family and to propose matters to be addressed in future studies. In the earlier sections of this review, we summarize the historical aspect of VP/OXT research as well as the basic features of hormonal peptides and corresponding receptors. The latter sections describe VP/OXT family peptides and their receptors in nonmammalian species, including invertebrates, to introduce the evolutionary aspect of this hormone family. By integrating knowledge from both general and comparative endocrinology perspectives, we highlight current and future research trends about the VP/OXT system.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171300"},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder 人类催产素受体的 R150S 突变:功能增益效应及其对自闭症谱系障碍的影响
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-10 DOI: 10.1016/j.peptides.2024.171301
Xiaoxi Liu , Stanislav Cherepanov , Mehdi Abouzari , Amila Zuko , Shu Yang , Jamasb Sayadi , Xiaoyuan Jia , Chikashi Terao , Tsukasa Sasaki , Shigeru Yokoyama
This study investigates the rs547238576 (R150S) missense variant in the oxytocin receptor (OXTR) gene, previously observed through screening of rare variants in Japanese individuals with autism spectrum disorders (ASD). Contrary to the anticipated loss-of-function, R150S exhibits gain-of-function effects, enhancing oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca2+ mobilization in vitro. This suggests R150S may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD and other psychiatric disorders. Our findings underscore the significance of genetic variations in OXTR on functional activity and highlight the necessity for population-specific genetic study and in vitro analysis to elucidate genetic susceptibilities to neuropsychiatric conditions.
本研究调查了催产素受体(OXTR)基因中的rs547238576(R150S)错义变异,该变异先前是通过筛查日本自闭症谱系障碍(ASD)患者中的罕见变异而发现的。与预期的功能缺失相反,R150S 表现出功能增益效应,在体外增强了催产素(OXT)的敏感性、配体结合亲和力和 OXT 诱导的 Ca2+ 调动。这表明 R150S 可能会改变 OXT 信号转导,从而可能导致 ASD 和其他精神疾病中出现的兴奋/抑制失衡。我们的研究结果强调了 OXTR 基因变异对功能活动的重要影响,并突出了进行特定人群基因研究和体外分析以阐明神经精神疾病遗传易感性的必要性。
{"title":"R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder","authors":"Xiaoxi Liu ,&nbsp;Stanislav Cherepanov ,&nbsp;Mehdi Abouzari ,&nbsp;Amila Zuko ,&nbsp;Shu Yang ,&nbsp;Jamasb Sayadi ,&nbsp;Xiaoyuan Jia ,&nbsp;Chikashi Terao ,&nbsp;Tsukasa Sasaki ,&nbsp;Shigeru Yokoyama","doi":"10.1016/j.peptides.2024.171301","DOIUrl":"10.1016/j.peptides.2024.171301","url":null,"abstract":"<div><div>This study investigates the rs547238576 (R150S) missense variant in the oxytocin receptor (<em>OXTR</em>) gene, previously observed through screening of rare variants in Japanese individuals with autism spectrum disorders (ASD). Contrary to the anticipated loss-of-function, R150S exhibits gain-of-function effects, enhancing oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca<sup>2+</sup> mobilization <em>in vitro</em>. This suggests R150S may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD and other psychiatric disorders. Our findings underscore the significance of genetic variations in <em>OXTR</em> on functional activity and highlight the necessity for population-specific genetic study and <em>in vitro</em> analysis to elucidate genetic susceptibilities to neuropsychiatric conditions.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171301"},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cholecystokinin regulates atrial natriuretic peptide secretion through activation of NOX4–Sirt1–LEF1 signaling in beating rat hypoxic atria 胆囊收缩素通过激活搏动大鼠缺氧心房中的 NOX4-Sirt1-LEF1 信号来调节心房利钠肽的分泌
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-24 DOI: 10.1016/j.peptides.2024.171299
Li-jia Xu , Meng-tao Zhi , Xiao-xue Lin , Xiang Li , Zhi-yu Li , Xun Cui
The mammalian cardiac myocytes not only synthesize and secrete atrial natriuretic peptide (ANP), but also express cholecystokinin (CCK) and its receptors (CCK1R and CCK2R). However, atrial CCK expression patterns and its effects on ANP secretion during hypoxia are unclear. Therefore, this study is aimed to investigate the effect of hypoxia on the expression levels of CCK and its receptors, as well as the underlying mechanisms involved in regulating hypoxia-induced ANP secretion in isolated beating atria. The results of this study showed that acute hypoxia significantly upregulated expression of CCK and CCK1R as well as CCK2R through activation of hypoxia-inducible factor 1α–apelin signaling. Endogenous CCK induced by hypoxia markedly upregulated the expression of silent information regulator factor 2-related enzyme 1 (Sirt1) and its downstream nuclear factor erythroid‑2‑related factor 2 (Nrf2) via the activation of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), leading to increase of activating T cell factor (TCF) 3 and TCF4/ lymphoid enhancer factor (LEF) 1, ultimately promoting hypoxia-induced ANP secretion. In addition, siRNA-mediated knockdown of LEF1 dramatically attenuated hypoxia-induced increase of ANP expression in HL-1 atrial myocytes. These results indicated endogenous CCK induced by hypoxia promoted hypoxia-induced ANP secretion by activation of NOX4–Sirt1–TCF3/4–LEF1 signaling pathway.
哺乳动物心肌细胞不仅能合成和分泌心房利钠肽(ANP),还能表达胆囊收缩素(CCK)及其受体(CCK1R 和 CCK2R)。然而,缺氧时心房 CCK 的表达模式及其对 ANP 分泌的影响尚不清楚。因此,本研究旨在探讨缺氧对离体搏动心房中 CCK 及其受体表达水平的影响,以及调节缺氧诱导 ANP 分泌的内在机制。研究结果表明,急性缺氧通过激活缺氧诱导因子1α-apelin信号传导,显著上调CCK和CCK1R以及CCK2R的表达。缺氧诱导的内源性CCK通过激活烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)显著上调沉默信息调节因子2相关酶1(Sirt1)及其下游核因子红细胞-2相关因子2(Nrf2)的表达,导致活化T细胞因子(TCF)3和TCF4/淋巴增强因子(LEF)1的增加,最终促进缺氧诱导的ANP分泌。此外,siRNA 介导的 LEF1 敲除可显著减少缺氧诱导的 HL-1 心房肌细胞 ANP 表达的增加。这些结果表明,缺氧诱导的内源性CCK通过激活NOX4-Sirt1-TCF3/4-LEF1信号通路促进缺氧诱导的ANP分泌。
{"title":"Cholecystokinin regulates atrial natriuretic peptide secretion through activation of NOX4–Sirt1–LEF1 signaling in beating rat hypoxic atria","authors":"Li-jia Xu ,&nbsp;Meng-tao Zhi ,&nbsp;Xiao-xue Lin ,&nbsp;Xiang Li ,&nbsp;Zhi-yu Li ,&nbsp;Xun Cui","doi":"10.1016/j.peptides.2024.171299","DOIUrl":"10.1016/j.peptides.2024.171299","url":null,"abstract":"<div><div>The mammalian cardiac myocytes not only synthesize and secrete atrial natriuretic peptide (ANP), but also express cholecystokinin (CCK) and its receptors (CCK<sub>1</sub>R and CCK<sub>2</sub>R). However, atrial CCK expression patterns and its effects on ANP secretion during hypoxia are unclear. Therefore, this study is aimed to investigate the effect of hypoxia on the expression levels of CCK and its receptors, as well as the underlying mechanisms involved in regulating hypoxia-induced ANP secretion in isolated beating atria. The results of this study showed that acute hypoxia significantly upregulated expression of CCK and CCK<sub>1</sub>R as well as CCK<sub>2</sub>R through activation of hypoxia-inducible factor 1α–apelin signaling. Endogenous CCK induced by hypoxia markedly upregulated the expression of silent information regulator factor 2-related enzyme 1 (Sirt1) and its downstream nuclear factor erythroid‑2‑related factor 2 (Nrf2) via the activation of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), leading to increase of activating T cell factor (TCF) 3 and TCF4/ lymphoid enhancer factor (LEF) 1, ultimately promoting hypoxia-induced ANP secretion. In addition, siRNA-mediated knockdown of LEF1 dramatically attenuated hypoxia-induced increase of ANP expression in HL-1 atrial myocytes. These results indicated endogenous CCK induced by hypoxia promoted hypoxia-induced ANP secretion by activation of NOX4–Sirt1–TCF3/4–LEF1 signaling pathway.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171299"},"PeriodicalIF":2.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of CART peptide in learning and memory: A potential therapeutic target in memory-related disorders CART 肽在学习和记忆中的作用:记忆相关疾病的潜在治疗靶点
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-22 DOI: 10.1016/j.peptides.2024.171298
Atefeh Bakhtazad , Mohamed Kabbaj , Behzad Garmabi , Mohammad Taghi Joghataei
Cocaine and amphetamine-regulated transcript (CART) mRNA and peptide are vastly expressed in both cortical and subcortical brain areas and are involved in critical cognitive functions. CART peptide (CARTp), described in reward-related brain structures, regulates drug-induced learning and memory, and its role appears specific to psychostimulants. However, many other drugs of abuse, such as alcohol, opiates, nicotine, and caffeine, have been shown to alter the expression levels of CART mRNA and peptides in brain structures directly or indirectly associated with learning and memory processes. However, the number of studies demonstrating the contribution of CARTp in learning and memory is still minimal. Notably, the exact cellular and molecular mechanisms underlying CARTp effects are still unknown. The discoveries that CARTp effects are mediated through a putative G-protein coupled receptor and activation of cellular signaling cascades via NMDA receptor-coupled ERK have enhanced our knowledge about the action of this neuropeptide and allowed us to comprehend better CARTp exact cellular/molecular mechanisms that could mediate drug-induced changes in learning and memory functions. Unfortunately, these efforts have been impeded by the lack of suitable and specific CARTp receptor antagonists.
In this review, following a short introduction about CARTp, we report on current knowledge about CART's roles in learning and memory processes and its recently described role in memory-related neurological disorders. We will also discuss the importance of further investigating how CARTp interacts with its receptor(s) and other neurotransmitter systems to influence learning and memory functions. This topic is sure to intrigue and motivate further exploration in the field of neuroscience.
可卡因和苯丙胺调节转录物(CART)mRNA和肽在大脑皮层和皮层下脑区均有大量表达,并参与重要的认知功能。CART 肽(CARTp)存在于与奖赏相关的大脑结构中,调节药物诱导的学习和记忆,其作用似乎是精神兴奋剂所特有的。然而,许多其他滥用药物,如酒精、鸦片制剂、尼古丁和咖啡因,已被证明会改变与学习和记忆过程直接或间接相关的大脑结构中 CART mRNA 和肽的表达水平。然而,证明 CARTp 在学习和记忆中的作用的研究仍然很少。值得注意的是,CARTp 作用的确切细胞和分子机制仍不为人知。CARTp 的作用是通过一种推定的 G 蛋白偶联受体介导的,并通过 NMDA 受体偶联 ERK 激活细胞信号级联,这些发现增进了我们对这种神经肽作用的了解,使我们能够更好地理解 CARTp 的确切细胞/分子机制,这些机制可能介导药物诱导的学习和记忆功能的变化。遗憾的是,由于缺乏合适的特异性 CARTp 受体拮抗剂,这些研究工作受到了阻碍。在这篇综述中,在简要介绍 CARTp 之后,我们将报告目前有关 CART 在学习和记忆过程中的作用以及最近描述的它在与记忆相关的神经系统疾病中的作用的知识。我们还将讨论进一步研究 CARTp 如何与其受体和其他神经递质系统相互作用以影响学习和记忆功能的重要性。这个话题一定会引起人们的兴趣,并促使人们在神经科学领域进行进一步的探索。
{"title":"The role of CART peptide in learning and memory: A potential therapeutic target in memory-related disorders","authors":"Atefeh Bakhtazad ,&nbsp;Mohamed Kabbaj ,&nbsp;Behzad Garmabi ,&nbsp;Mohammad Taghi Joghataei","doi":"10.1016/j.peptides.2024.171298","DOIUrl":"10.1016/j.peptides.2024.171298","url":null,"abstract":"<div><div>Cocaine and amphetamine-regulated transcript (CART) mRNA and peptide are vastly expressed in both cortical and subcortical brain areas and are involved in critical cognitive functions. CART peptide (CARTp), described in reward-related brain structures, regulates drug-induced learning and memory, and its role appears specific to psychostimulants. However, many other drugs of abuse, such as alcohol, opiates, nicotine, and caffeine, have been shown to alter the expression levels of CART mRNA and peptides in brain structures directly or indirectly associated with learning and memory processes. However, the number of studies demonstrating the contribution of CARTp in learning and memory is still minimal. Notably, the exact cellular and molecular mechanisms underlying CARTp effects are still unknown. The discoveries that CARTp effects are mediated through a putative G-protein coupled receptor and activation of cellular signaling cascades via NMDA receptor-coupled ERK have enhanced our knowledge about the action of this neuropeptide and allowed us to comprehend better CARTp exact cellular/molecular mechanisms that could mediate drug-induced changes in learning and memory functions. Unfortunately, these efforts have been impeded by the lack of suitable and specific CARTp receptor antagonists.</div><div>In this review, following a short introduction about CARTp, we report on current knowledge about CART's roles in learning and memory processes and its recently described role in memory-related neurological disorders. We will also discuss the importance of further investigating how CARTp interacts with its receptor(s) and other neurotransmitter systems to influence learning and memory functions. This topic is sure to intrigue and motivate further exploration in the field of neuroscience.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171298"},"PeriodicalIF":2.8,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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
Peptides
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:604180095
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