PeptidesPub Date : 2025-01-01DOI: 10.1016/j.peptides.2024.171325
Marcela Cristina Garnica-Siqueira , Andressa Busetti Martins , Érica Cristina Alves Munhoz Monteiro , Maria Heloisa Bernardes de Oliveira , Carolina dos Reis Baratto , Fabiano Takeo Komay Tsutsui , Lucas Leonardo França de Oliveira , Larissa Rugila dos Santos Stopa , Camila Franciele de Souza , Ana Luiza Machado Wunderlich , Dimas Augusto Morozin Zaia , Cristiane Mota Leite , Cássia Thaïs Bussamra Vieira Zaia , Ernane Torres Uchoa
{"title":"Estrogens impair hypophagia and hypothalamic cell activation induced by vasoactive intestinal peptide, but not by pituitary adenylate cyclase-activating polypeptide","authors":"Marcela Cristina Garnica-Siqueira , Andressa Busetti Martins , Érica Cristina Alves Munhoz Monteiro , Maria Heloisa Bernardes de Oliveira , Carolina dos Reis Baratto , Fabiano Takeo Komay Tsutsui , Lucas Leonardo França de Oliveira , Larissa Rugila dos Santos Stopa , Camila Franciele de Souza , Ana Luiza Machado Wunderlich , Dimas Augusto Morozin Zaia , Cristiane Mota Leite , Cássia Thaïs Bussamra Vieira Zaia , Ernane Torres Uchoa","doi":"10.1016/j.peptides.2024.171325","DOIUrl":"10.1016/j.peptides.2024.171325","url":null,"abstract":"<div><div>The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) act in arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei, reducing food intake and changing plasma parameters. Estrogens (E) also regulate energy homeostasis, and loss of ovarian function leads to hyperphagia and body weight gain. This study aimed to evaluate the effects of estradiol (E) in a postmenopausal rat model, ovariectomy (OVX), on PAC1 and VPAC2 receptors in the PVN and ARC, as well as on food intake, plasma parameters, and PVN and ARC cell activation in response to intracerebroventricular microinjection of VIP and PACAP. For this, the rats underwent intracerebroventricular and OVX surgeries, being treated daily with subcutaneous injections of 0.2 mL of corn oil or 10 μg/0.2 mL of estradiol cypionate, comprising the OVX+O and OVX+E groups, respectively. OVX+E showed reduced VPAC2 mRNA expression in the PVN. PACAP reduced food intake in both groups, and VIP-induced hypophagia was not observed in OVX+E. VIP increased plasma glucose in both groups, and PACAP increased plasma glucose only in OVX+O. VIP decreased free fatty acids in OVX+E. Furthermore, PACAP increased ARC cell activation in both groups, and in the PVN only in OVX+O. Cell activation induced by VIP in ARC and PVN was blocked by estradiol. Therefore, estrogens disrupted the hypophagia induced by VIP, but not by PACAP, and these differences seem to be, at least in part, due to an impairment of the activation of the ARC-PVN pathway.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"183 ","pages":"Article 171325"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771185","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 : 2025-01-01DOI: 10.1016/j.peptides.2024.171336
Yuchen Xie , Yihui Feng , Shaohua Li , Bowen Yu , Fangzheng Yang , Yanfei Li , Yuanchao Cheng , Zhouxi Yu , Chanjuan Li , Jing Dong , Junhua Yuan
{"title":"Nesfatin-1 is involved in hyperbaric oxygen-mediated therapeutic effects in high fat diet-induced hyperphagia in mice","authors":"Yuchen Xie , Yihui Feng , Shaohua Li , Bowen Yu , Fangzheng Yang , Yanfei Li , Yuanchao Cheng , Zhouxi Yu , Chanjuan Li , Jing Dong , Junhua Yuan","doi":"10.1016/j.peptides.2024.171336","DOIUrl":"10.1016/j.peptides.2024.171336","url":null,"abstract":"<div><div>Obesity is a worldwide health issue. Effective and safe methods for obesity management are highly desirable. In the current study, hyperbaric oxygen (HBO) treatment was investigated as a potential treatment against obesity-associated hyperphagia and hyperenergy intake. Diet induced obesity (DIO) mice model was established with high fat diet (HFD) feeding, HBO was then co-administered. Food and energy intake were assessed with nocturnal food intake assay. Immunohistochemistry for c-Fos was performed for neuronal activation in arcuate nucleus (ARC), paraventricular nucleus of hypothalamus (PVN) and lateral parabrachial nucleus (LPBN) of brain. Additionally, enzyme-linked immunosorbent assay (ELISA) in serum and immunofluorescence in LPBN were performed. Results indicated that HBO co-treatment effectively decreased food and energy intake in DIO mice, reverted the abnormal neuronal activation in the ARC and PVN, and enhanced both peripheral and central nesfatin-1 peptide levels without affecting serum leptin levels. While SHU9119 microinjection in LPBN effectively abolished the beneficial effects of HBO on body weight, visceral fat, nocturnal feeding and energy intake in DIO mice. In conclusion, HBO treatment could effectively protect against HFD-induced increase of food and energy intake, which is associated with its central effects against abnormal neuronal activation in ARC and PVN and enhanced peptide levels of nesfatin-1 both centrally and peripherally. The melanocortin system downstream of nesfatin-1 may exert a potential effect in this process.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"183 ","pages":"Article 171336"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872364","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 : 2025-01-01DOI: 10.1016/j.peptides.2024.171339
Ida Stangerup , Birgitte Georg , Jens Hannibal
{"title":"Prokineticin 2 protein is diurnally expressed in PER2-containing clock neurons in the mouse suprachiasmatic nucleus","authors":"Ida Stangerup , Birgitte Georg , Jens Hannibal","doi":"10.1016/j.peptides.2024.171339","DOIUrl":"10.1016/j.peptides.2024.171339","url":null,"abstract":"<div><div>Expression of prokineticin 2 (PK2) mRNA in the suprachiasmatic nucleus (SCN), also known as the brain’s clock, exhibits circadian oscillations with peak levels midday, zeitgeber time (ZT) 4, and almost undetectable levels during night. This circadian expression profile has substantially contributed to the suggested role of PK2 as an SCN output molecule involved in transmitting circadian rhythm of behavior and physiology. Due to unreliable specificity of PK2 antibodies, the 81 amino acid protein has primarily been studied at the mRNA level and correlation between circadian oscillating mRNAs and protein products are infrequent. Hence, data on PK2 protein expression in the SCN is lacking. In this study a thorough validation of a commercial PK2 antibody for immunohistochemistry (IHC) was performed followed by fluorescence IHC on SCN mouse brain sections at six consecutive ZTs over a 24-h cycle (12:12 light-dark, ZT0 =light ON whereas ZT12 =light OFF). Data were visualized and processed using confocal microscopy. Results showed that PK2 protein expression diurnally oscillates with calculated peak expression ZT5:40 ± 1:40 h. Opposite than described for PK2 mRNA, PK2 immunoreactivity was detectable at all times during the 24-h cycle. PK2 was primarily located in neurons of the shell compartment and > 80 % of these neurons co-expressed the core clock protein PER2. In conclusion, PK2 protein expression oscillates as the mRNA, supporting the suggested role of PK2 as a SCN molecule involved in circadian rhythm regulation.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"183 ","pages":"Article 171339"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927644","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}
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.2024.171324
Karl-Heinz Herzig
{"title":"The Viktor Mutt Award Lecture 2024 to Tomas Hökfelt","authors":"Karl-Heinz Herzig","doi":"10.1016/j.peptides.2024.171324","DOIUrl":"10.1016/j.peptides.2024.171324","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"182 ","pages":"Article 171324"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","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}
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}
{"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}