PeptidesPub Date : 2024-02-05DOI: 10.1016/j.peptides.2024.171168
Clifford J. Bailey , Peter R. Flatt
{"title":"Duodenal enteroendocrine cells and GIP as treatment targets for obesity and type 2 diabetes","authors":"Clifford J. Bailey , Peter R. Flatt","doi":"10.1016/j.peptides.2024.171168","DOIUrl":"10.1016/j.peptides.2024.171168","url":null,"abstract":"<div><p>The duodenum is an important source of endocrine and paracrine signals controlling digestion and nutrient disposition, notably including the main incretin hormone glucose-dependent insulinotropic polypeptide (GIP). Bariatric procedures that prevent nutrients from contact with the duodenal mucosa are particularly effective interventions to reduce body weight and improve glycaemic control in obesity and type 2 diabetes. These procedures take advantage of increased nutrient delivery to more distal regions of the intestine which enhances secretion of the other incretin hormone glucagon-like peptide-1 (GLP-1). Preclinical experiments have shown that either an increase or a decrease in the secretion or action of GIP can decrease body weight and blood glucose in obesity and non-insulin dependent hyperglycaemia, but clinical studies involving administration of GIP have been inconclusive. However, a synthetic dual agonist peptide (tirzepatide) that exerts agonism at receptors for GIP and GLP-1 has produced marked weight-lowering and glucose-lowering effects in people with obesity and type 2 diabetes. This appears to result from chronic biased agonism in which the novel conformation of the peptide triggers enhanced signalling by the GLP-1 receptor through reduced internalisation while reducing signalling by the GIP receptor directly or via functional antagonism through increased internalisation and degradation.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"174 ","pages":"Article 171168"},"PeriodicalIF":3.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139683155","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":"Therapeutic potential of vasopressin in the treatment of neurological disorders","authors":"Shweta Mishra , Jyoti Grewal , Pranay Wal , Gauri U. Bhivshet , Arpan Kumar Tripathi , Vaibhav Walia","doi":"10.1016/j.peptides.2024.171166","DOIUrl":"10.1016/j.peptides.2024.171166","url":null,"abstract":"<div><p>Vasopressin (VP) is a nonapeptide made of nine amino acids synthesized by the hypothalamus and released by the pituitary gland. VP acts as a neurohormone, neuropeptide and neuromodulator and plays an important role in the regulation of water balance, osmolarity, blood pressure, body temperature, stress response, emotional challenges, etc. Traditionally VP is known to regulate the osmolarity and tonicity. VP and its receptors are widely expressed in the various region of the brain including cortex, hippocampus, basal forebrain, amygdala, etc. VP has been shown to modulate the behavior, stress response, circadian rhythm, cerebral blood flow, learning and memory, etc. The potential role of VP in the regulation of these neurological functions have suggested the therapeutic importance of VP and its analogues in the management of neurological disorders. Further, different VP analogues have been developed across the world with different pharmacotherapeutic potential. In the present work authors highlighted the therapeutic potential of VP and its analogues in the treatment and management of various neurological disorders.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"174 ","pages":"Article 171166"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681346","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 : 2024-02-01DOI: 10.1016/j.peptides.2024.171165
Hana Ujcikova , Yeon Sun Lee , Lenka Roubalova , Petr Svoboda
{"title":"The impact of multifunctional enkephalin analogs and morphine on the protein changes in crude membrane fractions isolated from the rat brain cortex and hippocampus","authors":"Hana Ujcikova , Yeon Sun Lee , Lenka Roubalova , Petr Svoboda","doi":"10.1016/j.peptides.2024.171165","DOIUrl":"10.1016/j.peptides.2024.171165","url":null,"abstract":"<div><p>Endogenous opioid peptides serve as potent analgesics through the opioid receptor (OR) activation. However, they often suffer from poor metabolic stability, low lipophilicity, and low blood-brain barrier permeability. Researchers have developed many strategies to overcome the drawbacks of current pain medications and unwanted biological effects produced by the interaction with opioid receptors. Here, we tested multifunctional enkephalin analogs <strong>LYS739</strong> (MOR/DOR agonist and KOR partial antagonist) and <strong>LYS744</strong> (MOR/DOR agonist and KOR full antagonist) under in vivo conditions in comparison with MOR agonist, morphine. We applied 2D electrophoretic resolution to investigate differences in proteome profiles of crude membrane (CM) fractions isolated from the rat brain cortex and hippocampus exposed to the drugs (10 mg/kg, seven days). Our results have shown that treatment with analog <strong>LYS739</strong> induced the most protein changes in cortical and hippocampal samples. The identified proteins were mainly associated with energy metabolism, cell shape and movement, apoptosis, protein folding, regulation of redox homeostasis, and signal transduction. Among these, the isoform of mitochondrial ATP synthase subunit beta (ATP5F1B) was the only protein upregulation in the hippocampus but not in the brain cortex. Contrarily, the administration of analog <strong>LYS744</strong> caused a small number of protein alterations in both brain parts. Our results indicate that the KOR full antagonism, together with MOR/DOR agonism of multifunctional opioid ligands, can be beneficial in treating chronic pain states by reducing changes in protein expression levels but retaining analgesic efficacy.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"174 ","pages":"Article 171165"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672347","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 : 2024-01-23DOI: 10.1016/j.peptides.2024.171164
Yaxing Wang, Zhuo Zuo, Jiajia Shi, Yanwei Fang, Zhongqian Yin, Zhe Wang, Zhouqi Yang, Bin Jia, Yulong Sun
{"title":"Modulatory role of neuropeptide FF system in macrophages","authors":"Yaxing Wang, Zhuo Zuo, Jiajia Shi, Yanwei Fang, Zhongqian Yin, Zhe Wang, Zhouqi Yang, Bin Jia, Yulong Sun","doi":"10.1016/j.peptides.2024.171164","DOIUrl":"10.1016/j.peptides.2024.171164","url":null,"abstract":"<div><p><span><span><span>Neuropeptide FF (NPFF) is an </span>octapeptide that regulates various cellular processes, especially </span>pain perception<span><span>. Recently, there has been a growing interest in understanding the modulation of NPFF in neuroendocrine inflammation. This review aims to provide a thorough overview of the regulation of NPFF in macrophage-mediated biological processes<span>. We delve into the impact of NPFF on macrophage polarization, self-renewal modulation, and the promotion of mitophagy, facilitating the transition from thermogenic fat to fat-storing </span></span>adipose tissue. Additionally, we explore the NPFF-dependent regulation of the inflammatory response mediated by macrophages, its impact on the differentiation of macrophages, and its capacity to induce alterations in the </span></span>transcriptome of macrophages. We also address the potential of NPFF as a therapeutic molecule in the field of neuroendocrine inflammation. Overall, our work offers an understanding of the influence of NPFF on macrophage, facilitating the exploration of its pharmacological significance in future studies.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"174 ","pages":"Article 171164"},"PeriodicalIF":3.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564621","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 : 2024-01-22DOI: 10.1016/j.peptides.2024.171155
Karl-Heinz Herzig
{"title":"The Viktor Mutt Award Lecture 2022 – Homage to an outstanding scientist","authors":"Karl-Heinz Herzig","doi":"10.1016/j.peptides.2024.171155","DOIUrl":"10.1016/j.peptides.2024.171155","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"174 ","pages":"Article 171155"},"PeriodicalIF":3.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139523150","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 : 2024-01-19DOI: 10.1016/j.peptides.2024.171156
Sarah Appleby , Hamish M. Aitken-Buck , Mark S. Holdaway , Mathew S. Byers , Chris M. Frampton , Louise N. Paton , A. Mark Richards , Regis R. Lamberts , Christopher J. Pemberton
{"title":"Cardiac effects of myoregulin in ischemia-reperfusion","authors":"Sarah Appleby , Hamish M. Aitken-Buck , Mark S. Holdaway , Mathew S. Byers , Chris M. Frampton , Louise N. Paton , A. Mark Richards , Regis R. Lamberts , Christopher J. Pemberton","doi":"10.1016/j.peptides.2024.171156","DOIUrl":"10.1016/j.peptides.2024.171156","url":null,"abstract":"<div><p>Myoregulin is a recently discovered micropeptide that controls calcium levels by inhibiting the intracellular calcium pump sarco-endoplasmic reticulum Ca<sup>2+</sup>-ATPase (SERCA). Keeping calcium levels balanced in the heart is essential for normal heart functioning, thus myoregulin has the potential to be a crucial regulator of cardiac muscle performance by reducing the rate of intracellular Ca<sup>2+</sup> uptake. We provide the first report of myoregulin mRNA expression in human heart tissue, absence of expression in human plasma, and the effects of myoregulin on cardiac hemodynamics in an <em>ex vivo</em> Langendorff isolated rat heart model of ischemia/reperfusion. In this preliminary study, myoregulin provided a cardio-protective effect, as assessed by preservation of left ventricular contractility and relaxation, during ischemia/reperfusion. This study provides the foundation for future research in this area.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"174 ","pages":"Article 171156"},"PeriodicalIF":3.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000093/pdfft?md5=305cdafdde109b6409307a34b1003857&pid=1-s2.0-S0196978124000093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513290","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 : 2024-01-17DOI: 10.1016/j.peptides.2024.171154
Zhineng Liu , Keyi Nong , Xinyun Qin , Xin Fang , Bin Zhang , Wanyan Chen , Zihan Wang , Yijia Wu , Huiyu Shi , Xuemei Wang , Youming Liu , Qingfeng Guan , Haiwen Zhang
{"title":"The antimicrobial peptide Abaecin alleviates colitis in mice by regulating inflammatory signaling pathways and intestinal microbial composition","authors":"Zhineng Liu , Keyi Nong , Xinyun Qin , Xin Fang , Bin Zhang , Wanyan Chen , Zihan Wang , Yijia Wu , Huiyu Shi , Xuemei Wang , Youming Liu , Qingfeng Guan , Haiwen Zhang","doi":"10.1016/j.peptides.2024.171154","DOIUrl":"10.1016/j.peptides.2024.171154","url":null,"abstract":"<div><p><span>Abaecin is a natural antimicrobial peptide (AMP) rich in </span>proline<span><span> from bees. It is an important part of the innate humoral immunity<span> of bees and has broad-spectrum antibacterial ability. This study aimed to determine the effect of Abaecin on dextran sulfate sodium (DSS) -induced ulcerative colitis (UC) in mice and to explore its related mechanisms. Twenty-four mice with similar body weight were randomly divided into 4 groups. 2.5% DSS was added to drinking water to induce colitis in mice. Abaecin and PBS were administered rectally on the third, fifth, and seventh days of the experimental period. The results showed that Abaecin significantly alleviated histological damage and </span></span>intestinal mucosal barrier<span><span> damage caused by colitis in mice, reduced the concentration of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ, and the phosphorylation of NF-κB / MAPK inflammatory </span>signaling pathway<span> proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC.</span></span></span></p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"173 ","pages":"Article 171154"},"PeriodicalIF":3.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502989","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 : 2024-01-12DOI: 10.1016/j.peptides.2024.171152
Longcheng Guo, Konstantin Stoffels, Jaap Broos, Oscar P. Kuipers
{"title":"Altering Specificity and Enhancing Stability of the Antimicrobial Peptides Nisin and Rombocin through Dehydrated Amino Acid Residue Engineering","authors":"Longcheng Guo, Konstantin Stoffels, Jaap Broos, Oscar P. Kuipers","doi":"10.1016/j.peptides.2024.171152","DOIUrl":"10.1016/j.peptides.2024.171152","url":null,"abstract":"<div><p>Nisin serves as the prototype within the lantibiotic group of antimicrobial peptides, exhibiting a broad-spectrum inhibition against Gram-positive bacteria, including important food-borne pathogens and clinically relevant antibiotic-resistant strains. The gene-encoded nature of nisin allows for gene-based bioengineering, enabling the generation of novel derivatives. It has been demonstrated that nisin mutants can be produced with improved functional properties. Here, we particularly focus on the uncommon amino acid residues dehydroalanine (Dha) and dehydrobutyrin (Dhb), whose functions are not yet fully elucidated. Prior to this study, we developed a new expression system that utilizes the nisin modification machinery NisBTC to advance expression, resulting in enhanced peptide dehydration efficiency. Through this approach, we discovered that the dehydrated amino acid Dhb at position 18 in the peptide rombocin, a short variant of nisin, displayed four times higher activity compared to the non-dehydrated peptide against the strain <em>Lactococcus lactis.</em> Furthermore, we observed that in the peptides nisin and rombocin, the dehydrated amino acid Dha at residue positon 18 exhibited superior activity compared to the dehydrated amino acid Dhb. Upon purifying the wild-type nisin and its variant nisinG18/Dha to homogeneity, the minimum inhibitory concentration (MIC) indicated that the variant exhibited activity similar to that of wild-type nisin in inhibiting the growth of <em>Bacillus cereus</em> but showed twice the MIC values against the other four tested Gram-positive strains. Further stability tests demonstrated that the dehydrated peptide exhibited properties similar to wild-type nisin under different temperatures but displayed higher resistance to proteolytic enzymes compared to wild-type nisin.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"174 ","pages":"Article 171152"},"PeriodicalIF":3.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000056/pdfft?md5=0bcb9d8132d8c50de32b65b2fea0cc15&pid=1-s2.0-S0196978124000056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139437852","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":"Simplified drug efficacy evaluation system for vasopressin neurodegenerative disease using mouse disease-specific induced pluripotent stem cells","authors":"Tsutomu Miwata , Hidetaka Suga , Kazuki Mitsumoto , Jun Zhang , Yoshimasa Hamada , Mayu Sakakibara , Mika Soen , Hajime Ozaki , Tomoyoshi Asano , Takashi Miyata , Yohei Kawaguchi , Yoshinori Yasuda , Tomoko Kobayashi , Mariko Sugiyama , Takeshi Onoue , Daisuke Hagiwara , Shintaro Iwama , Seiichi Oyadomari , Hiroshi Arima","doi":"10.1016/j.peptides.2024.171151","DOIUrl":"10.1016/j.peptides.2024.171151","url":null,"abstract":"<div><p><span>Familial neurohypophyseal diabetes insipidus<span><span><span> (FNDI) is a degenerative disorder in which vasopressin-secreting neurons degenerate over time due to the production of mutant proteins. We have demonstrated therapeutic effects of </span>chemical chaperones in an FNDI mouse model, but the complexity and length of this evaluation were problematic. In this study, we established disease-specific mouse </span>induced pluripotent stem cells<span> (iPSCs) from FNDI-model mice and differentiated vasopressin<span> neurons that produced mutant proteins. Fluorescence immunostaining showed that chemical chaperones appeared to protect vasopressin neurons generated from iPSCs derived from FNDI-model mice. Although KCL stimulation released vasopressin hormone from vasopressin neurons generated from FNDI-derived iPSCs, vasopressin hormone levels did not differ significantly between baseline and chaperone-added culture. Semi-quantification of vasopressin </span></span></span></span>carrier protein and mutant protein volumes in vasopressin neurons confirmed that chaperones exerted a therapeutic effect. This research provides fundamental technology for creating in vitro disease models using human iPSCs and can be applied to therapeutic evaluation of various degenerative diseases that produce abnormal proteins.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"173 ","pages":"Article 171151"},"PeriodicalIF":3.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432917","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}