Pub Date : 2024-10-24DOI: 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}
Pub Date : 2024-10-24DOI: 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.
{"title":"Nesfatin-1 expressed in human endometrial stromal cell line (THESC) stimulates decidualization through FAK/PI3K/AKT signaling pathway","authors":"Jinah Ha, 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}
Pub Date : 2024-10-18DOI: 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.
{"title":"Membrane alteration, anti-virulence properties and metabolomic perturbation of a chionodracine-derived antimicrobial peptide, KHS-Cnd, on two bacteria models","authors":"Esther Imperlini , Federica Massaro , Angelica Grifoni , Francesco Maiurano , Anna Rita Taddei , Stefano Borocci , Francesco Buonocore , 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}
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.
{"title":"Structure and function of neurohypophysial hormones","authors":"Yasumasa Iwasaki , Yoko Yamaguchi , 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}
Pub Date : 2024-10-10DOI: 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.
{"title":"R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder","authors":"Xiaoxi Liu , Stanislav Cherepanov , Mehdi Abouzari , Amila Zuko , Shu Yang , Jamasb Sayadi , Xiaoyuan Jia , Chikashi Terao , Tsukasa Sasaki , 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}
Pub Date : 2024-09-24DOI: 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.
{"title":"Cholecystokinin regulates atrial natriuretic peptide secretion through activation of NOX4–Sirt1–LEF1 signaling in beating rat hypoxic atria","authors":"Li-jia Xu , Meng-tao Zhi , Xiao-xue Lin , Xiang Li , Zhi-yu Li , 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}
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.
{"title":"The role of CART peptide in learning and memory: A potential therapeutic target in memory-related disorders","authors":"Atefeh Bakhtazad , Mohamed Kabbaj , Behzad Garmabi , 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}
Pub Date : 2024-09-10DOI: 10.1016/j.peptides.2024.171296
Christoffer Novais de Farias Silva , Amanda de Sá Martins de Bessa , Jaqueline Moura da Costa , Paulo Ricardo Lopes , Ângela Ribeiro Neves , Monique Machado Louredo Teles Bombardelli , Diego Basile Colugnati , Gustavo Rodrigues Pedrino , Elizabeth Pereira Mendes , Robson Augusto Sousa dos Santos , Manoel Francisco Biancardi , Fernanda Cristina Alcantara dos Santos , Carlos Henrique Castro
Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1–7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120 µg/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes.
{"title":"Mas receptor blockade impairs exercise-induced cardiac hypertrophy","authors":"Christoffer Novais de Farias Silva , Amanda de Sá Martins de Bessa , Jaqueline Moura da Costa , Paulo Ricardo Lopes , Ângela Ribeiro Neves , Monique Machado Louredo Teles Bombardelli , Diego Basile Colugnati , Gustavo Rodrigues Pedrino , Elizabeth Pereira Mendes , Robson Augusto Sousa dos Santos , Manoel Francisco Biancardi , Fernanda Cristina Alcantara dos Santos , Carlos Henrique Castro","doi":"10.1016/j.peptides.2024.171296","DOIUrl":"10.1016/j.peptides.2024.171296","url":null,"abstract":"<div><p>Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1–7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120 µg/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171296"},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241721","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}
Pub Date : 2024-09-10DOI: 10.1016/j.peptides.2024.171294
Patricia Ribeiro de Carvalho França , João Pedro Barros de Paiva , Rosangela Ribeiro de Carvalho , Claudia Pinto Figueiredo , Pierre Sirois , Patricia Dias Fernandes
Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues outside of the uterine cavity. Currently available drugs are efficacious in treating endometriosis-related pain, however it’s not a targeted treatment. The aim of this work is to evaluate the effects of R-954, a bradykinin B1 receptor antagonist, in a murine model of endometriosis. The model was induced in animals through autologous transplantation of part of the uterine horn. After 51 days, it was observed that implants developed into endometriotic lesions. The administration of R-954 or progesterone, for 15 consecutive days, prevented the progression of cyst development, reduced the size and weight of the cysts. Both treatments also reduced cellular infiltrate and production of inflammatory mediators (interleukin-1β, interleukin-6, tumor necrosis factor). However, only R-954 decreased angiogenic factors (VEGF and VEGF receptor). In addition, treatment with the antagonist did not interfere in the females’ estrous cycle, as well as prevented gestational losses (reduction in the number of intermediate resorptions in pregnant females with endometriosis). Data suggested that R-954 has anti-inflammatory and anti-angiogenic effects; does not influence the estrous cycle; and prevents the number of gestational losses suggesting it as a good candidate for endometriosis treatment.
{"title":"R-954, a bradykinin B1 receptor antagonist, as a potential therapy in a preclinical endometriosis model","authors":"Patricia Ribeiro de Carvalho França , João Pedro Barros de Paiva , Rosangela Ribeiro de Carvalho , Claudia Pinto Figueiredo , Pierre Sirois , Patricia Dias Fernandes","doi":"10.1016/j.peptides.2024.171294","DOIUrl":"10.1016/j.peptides.2024.171294","url":null,"abstract":"<div><p>Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues outside of the uterine cavity. Currently available drugs are efficacious in treating endometriosis-related pain, however it’s not a targeted treatment. The aim of this work is to evaluate the effects of R-954, a bradykinin B1 receptor antagonist, in a murine model of endometriosis. The model was induced in animals through autologous transplantation of part of the uterine horn. After 51 days, it was observed that implants developed into endometriotic lesions. The administration of R-954 or progesterone, for 15 consecutive days, prevented the progression of cyst development, reduced the size and weight of the cysts. Both treatments also reduced cellular infiltrate and production of inflammatory mediators (interleukin-1β, interleukin-6, tumor necrosis factor). However, only R-954 decreased angiogenic factors (VEGF and VEGF receptor). In addition, treatment with the antagonist did not interfere in the females’ estrous cycle, as well as prevented gestational losses (reduction in the number of intermediate resorptions in pregnant females with endometriosis). Data suggested that R-954 has anti-inflammatory and anti-angiogenic effects; does not influence the estrous cycle; and prevents the number of gestational losses suggesting it as a good candidate for endometriosis treatment.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"181 ","pages":"Article 171294"},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232351","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}
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