PeptidesPub Date : 2024-12-01DOI: 10.1016/j.peptides.2024.171323
Yuqiao Yang , Jin Liu , Lingyan Wang , Wen Wu, Quan Wang, Yu Zhao, Xi Qian, Zhuoran Wang, Na Fu, Yanqiong Wang, Jinqiao Qian
{"title":"Oxytocin attenuates cardiac hypertrophy by improving cardiac glucose metabolism and regulating OXTR/JAK2/STAT3 axis","authors":"Yuqiao Yang , Jin Liu , Lingyan Wang , Wen Wu, Quan Wang, Yu Zhao, Xi Qian, Zhuoran Wang, Na Fu, Yanqiong Wang, Jinqiao Qian","doi":"10.1016/j.peptides.2024.171323","DOIUrl":"10.1016/j.peptides.2024.171323","url":null,"abstract":"<div><h3>Background</h3><div>The progress of cardiac hypertrophy is modulated by JAK2/STAT3 signaling pathway. Cardiac glucose metabolism derangement exacerbates the progression of cardiac hypertrophy. Oxytocin (OT) has emerged as a significant hormone involved in cardiovascular homeostasis, especially in protecting against cardiac hypertrophy. The present study aims to explore whether the anti-hypertrophy effect of oxytocin is related to the JAK2/STAT3 signaling pathway and cardiac glucose metablism.</div></div><div><h3>Methods</h3><div>Cardiac hypertrophy model was induced by angiotensin II (Ang II) in H9c2 cells and in mice with or without oxytocin treatment. Changes in cardiac histopathology were evaluated by hematoxylin and eosin (H&E), Masson staining, and wheat germ agglutinin (WGA) staining. The hypertrophy-related genes and JAK2/STAT3 pathway signaling molecules were analyzed by qRT-PCR and western blotting. The levels of glucose, pyruvic acid, lactic acid, and lactate dehydrogenase activity in H9c2 cells using the corresponding assay kits.</div></div><div><h3>Results</h3><div>The results showed that OT inhibited hypertrophic and fibrotic changes. Furthermore, OT increased intracellular levels of glucose and pyruvic acid, and decreased lactate dehydrogenase activity and lactic acid levels. Mechanistically, Ang II decreased oxytocin receptors (OXTR) expression and facilitated JAK2 and STAT3 phosphorylation. OT treatment increased OXTR expression and blocked JAK2 and STAT3 phosphorylation The OXTR-specific siRNA-mediated depleted expression could abrogate OT-induced anti-hypertrophic effects in H9c2 cells following angiotensin II insult. However, the JAK2/STAT3 inhibitor AG490 rescued the protective effects of OT against cardiac hypertrophy under OXTR downregulation.</div></div><div><h3><strong>Conclusion</strong></h3><div>OT exerts its protective effects against cardiac hypertrophy by improving cardiac glucose metabolism and regulating OXTR/JAK2/STAT3 axis.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171323"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746871","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}
PeptidesPub Date : 2024-12-01DOI: 10.1016/j.peptides.2024.171322
Patrícia Tancsics , Aliz Kovács , Miklós Palotai , Zsolt Bagosi
{"title":"The effects of corticotropin-releasing factor (CRF) and urocortins on the noradrenaline (NA) released from the locus coeruleus (LC)","authors":"Patrícia Tancsics , Aliz Kovács , Miklós Palotai , Zsolt Bagosi","doi":"10.1016/j.peptides.2024.171322","DOIUrl":"10.1016/j.peptides.2024.171322","url":null,"abstract":"<div><div>Corticotropin-releasing factor (CRF) activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates the noradrenergic neurotransmission, both processes being implicated in the pathogenesis of anxiety and depression, but the intimate site and mechanism of interaction of CRF and CRF-related peptides, named urocortins (UCN1, UCN2, UCN3), with noradrenaline (NA) was not fully elucidated yet. Therefore, the aim of the present study was to investigate the actions of CRF and urocortins on the NA released from the rat locus coeruleus (LC), the primary source of NA in the brain, and the participation of CRF receptors (CRF1 and CRF2) in these actions. In order to do so, male Wistar rats were used, their LC were isolated and dissected, and the LC slices were incubated with tritium-labelled NA, superfused and stimulated electrically. During superfusion, the LC slices were treated with CRF, UCN1, UCN2 or UCN3, and, when significant effect was observed, pretreated with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B. The release of tritium-labelled NA from the LC was determined by liquid scintillation counting. CRF and UCN1 increased significantly the tritium-labelled NA release from the LC, and these effects were reduced by antalarmin, but not by astressin2B. In addition, UCN2, but not UCN3, decreased significantly the tritium-labelled NA release from the LC, and this effect was reversed by astressin2B, but not antalarmin. Our results indicate the existence of two apparently opposing CRF systems in the LC, since activation of CRF1 by CRF and UCN1 stimulated, whereas activation of CRF2 by UCN2 inhibited the NA release.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171322"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710638","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}
PeptidesPub Date : 2024-11-25DOI: 10.1016/j.peptides.2024.171324
Karl-Heinz Herzig
{"title":"The Viktor Mutt Award Lecture 2024 to Thomas Hökfelt.","authors":"Karl-Heinz Herzig","doi":"10.1016/j.peptides.2024.171324","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171324","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":" ","pages":"171324"},"PeriodicalIF":2.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739653","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}
{"title":"Host defense peptides at the crossroad of endothelial cell physiology: Insight into mechanistic and pharmacological implications","authors":"Vivek Kumar Garg , Hemant Joshi , Amarish Kumar Sharma , Kiran Yadav , Vikas Yadav","doi":"10.1016/j.peptides.2024.171320","DOIUrl":"10.1016/j.peptides.2024.171320","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs), particularly host defense peptides (HDPs), have gained recognition for their role in host defense mechanisms, but they have also shown potential as a promising anticancer, antiviral, antiparasitic, antifungal and immunomodulatory agent. Research studies in recent years have shown HDPs play a crucial role in endothelial cell function and biology. The function of endothelial cells is impacted by HDPs’ complex interplay between cytoprotective and cytotoxic actions as they are known to modulate barrier integrity, inflammatory response and angiogenesis. This biphasic response varies and depends on the peptide structure, its concentration, and the microenvironment. These effects are mediated through key signaling pathways, including MAPK, NF-κB, and PI3K/Akt, which controls responses such as cell proliferation, apoptosis, and migration. In the present review, we have discussed the significance of the intriguing relationship between HDPs and endothelial cell physiology which suggests it potential as a therapeutic agents for the treating wounds, cardiovascular diseases, and inflammation-related endothelial damage.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171320"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638462","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}
PeptidesPub Date : 2024-11-06DOI: 10.1016/j.peptides.2024.171319
J. Michael Conlon, Peter R. Flatt
{"title":"Discovery of the bioactive form of glucagon-like peptide-1: An attempt to correct some misconceptions","authors":"J. Michael Conlon, Peter R. Flatt","doi":"10.1016/j.peptides.2024.171319","DOIUrl":"10.1016/j.peptides.2024.171319","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171319"},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625721","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}
PeptidesPub Date : 2024-11-01DOI: 10.1016/j.peptides.2024.171317
Othman Al Musaimi
{"title":"Lasso peptides realm: Insights and applications","authors":"Othman Al Musaimi","doi":"10.1016/j.peptides.2024.171317","DOIUrl":"10.1016/j.peptides.2024.171317","url":null,"abstract":"<div><div>Lasso peptides exhibit a range of bioactivities, including antiviral effects, inhibition of the glucagon receptor, blockade of the endothelin type B receptor, inhibition of myosin light chain kinase, and modulation of the atrial natriuretic factor, as well as notable antimicrobial properties. Intriguingly, lasso peptides exhibit remarkable proteolytic and thermal stability, addressing one of the key challenges that traditional peptides often face. The challenge in producing those valuable peptides remains the main hurdle in the way of producing larger quantities or even modifying them with more potent analogues. Genome mining and heterologous expression approaches have greatly facilitated the production of lasso peptides, moving beyond mere isolation techniques. This advancement not only allows for larger quantities but also enables the creation of additional analogues with improved stability and potency. This review aims to explore the unique bioactivities and stability of lasso peptides, along with recent advancements in genome mining and heterologous expression that address production challenges and open pathways for engineering potent analogues.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171317"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569247","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}
{"title":"Maternal separation alters peripheral immune responses associated with IFN-γ and OT in mice","authors":"Yishu Zhang , HaiChao Chen , JiaXin Cao , LiPing Gao , YuHong Jing","doi":"10.1016/j.peptides.2024.171318","DOIUrl":"10.1016/j.peptides.2024.171318","url":null,"abstract":"<div><div>The co-evolution of social behavior and the immune system plays a critical role in individuals' adaptation to their environment. However, also need for further research on the key molecules that co-regulate social behavior and immunity. This study focused on neonatal mice that were separated from their mothers for 4 hours per day between the 6th and 16th day after birth. The results showed that these mice had lower plasma levels of IFN-γ and oxytocin, but higher levels of plasma glucocorticoids (GC), then impacting their social abilities. Additionally, maternal separation led to decreased levels of <em>BDNF</em>, <em>IGF2</em>, and <em>CREB</em> mRNAs in the hippocampus, while levels in the prefrontal cortex (PFC) remained unaffected. Maternal separation also resulted in increased levels of oxytocin and <em>CRH</em> mRNA in the hypothalamus, as well as an increase in CD45<sup>+</sup> lymphocyte subsets in the meninges and choroid plexus (CP), with CD8<sup>+</sup> lymphocytes in meninges and CD4<sup>+</sup> lymphocytes in CP showing an increase. In IFN-γ<sup>-/-</sup> mice, a decrease in social preference was observed alongside lower plasma oxytocin levels. Moreover, IFN-γ<sup>-/-</sup> mice exhibited reduced numbers of oxytocin neurons in the paraventricular nucleus of the paraventricular nucleus of hypothalamus (PVN), decreased <em>BDNF</em> levels in the PFC and hippocampus, and alterations in CD45<sup>+</sup> lymphocytes in CP and meninges, with an increase in CD8<sup>+</sup> lymphocytes in meninges and CD4<sup>+</sup> lymphocytes in CP. These findings highlight the immunological impact of social stress on IFN-γ regulation, suggesting that the immunomodulatory molecule IFN-γ may influence social behavior by affecting synaptic efficiency in brain regions such as the hippocampus and PFC, which are linked to oxytocin in the PVN.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171318"},"PeriodicalIF":2.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564342","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}
PeptidesPub Date : 2024-10-28DOI: 10.1016/j.peptides.2024.171312
Trinidad de los Ángeles Cordero Gil , María Soledad Moleón , Belkis Ester Marelli , Pablo Ariel Siroski
{"title":"Host defense peptides in crocodilians – A comprehensive review","authors":"Trinidad de los Ángeles Cordero Gil , María Soledad Moleón , Belkis Ester Marelli , 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}
PeptidesPub Date : 2024-10-26DOI: 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
{"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 , 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","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}