Pub Date : 2025-01-01Epub Date: 2024-11-29DOI: 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
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.
{"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}
Pub Date : 2025-01-01Epub Date: 2024-12-18DOI: 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
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.
{"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}
Pub Date : 2025-01-01Epub Date: 2025-01-02DOI: 10.1016/j.peptides.2024.171339
Ida Stangerup , Birgitte Georg , Jens Hannibal
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.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-11-01DOI: 10.1016/j.peptides.2024.171317
Othman Al Musaimi
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.
拉索肽具有一系列生物活性，包括抗病毒作用、抑制胰高血糖素受体、阻断 B 型内皮素受体、抑制肌球蛋白轻链激酶、调节心房利钠因子，以及显著的抗微生物特性。有趣的是，拉索肽具有显著的蛋白水解稳定性和热稳定性，解决了传统多肽经常面临的关键挑战之一。生产这些有价值的多肽所面临的挑战仍然是生产更多甚至用更强效的类似物对其进行改良的主要障碍。基因组挖掘和异源表达方法大大促进了套索肽的生产，超越了单纯的分离技术。这一进步不仅可以生产更多数量的拉索肽，还能创造出更多具有更高稳定性和效力的类似物。
{"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":"2024-12-01","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}
Pub Date : 2024-12-01Epub Date: 2024-11-28DOI: 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
Background
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.
Methods
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.
Results
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.
Conclusion
OT exerts its protective effects against cardiac hypertrophy by improving cardiac glucose metabolism and regulating OXTR/JAK2/STAT3 axis.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-11-26DOI: 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}
Pub Date : 2024-12-01Epub 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":"2024-12-01","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}
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.
{"title":"Suppression of B-type natriuretic peptide gene expression in cardiomyocytes under anoxic conditions","authors":"Rei Yasutake, Tomohisa Nagoshi, Akira Yoshii, Hirotake Takahashi, Yuhei Oi, Haruka Kimura, Yusuke Kashiwagi, Toshikazu D. Tanaka, Yoshiro Tanaka, 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":"2024-12-01","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}
Pub Date : 2024-12-01Epub 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":"2024-12-01","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}
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