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Cardiac effects of myoregulin in ischemia-reperfusion 肌球蛋白在缺血再灌注中对心脏的影响

IF 3 4区医学

Peptides Pub Date : 2024-01-19 DOI: 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>Myoregulin is a recently discovered micropeptide that controls calcium levels by inhibiting the intracellular calcium pump sarco-endoplasmic reticulum Ca2+-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 Ca2+ 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 ex vivo 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.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"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}

引用次数: 0

The antimicrobial peptide Abaecin alleviates colitis in mice by regulating inflammatory signaling pathways and intestinal microbial composition 抗菌肽阿贝金通过调节炎症信号通路和肠道微生物组成缓解小鼠结肠炎。

IF 3 4区医学

Peptides Pub Date : 2024-01-17 DOI: 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>Abaecin is a natural antimicrobial peptide (AMP) rich in proline from bees. It is an important part of the innate humoral immunity 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 intestinal mucosal barrier 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 signaling pathway proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"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}

引用次数: 0

Orexin/hypocretin 编辑：Orexin/Hypocretin。

IF 3 4区医学

Peptides Pub Date : 2024-01-14 DOI: 10.1016/j.peptides.2024.171153

Tomoyuki Kuwaki

引用次数: 0

Altering Specificity and Enhancing Stability of the Antimicrobial Peptides Nisin and Rombocin through Dehydrated Amino Acid Residue Engineering 通过脱水氨基酸残基工程改变抗菌肽 Nisin 和 Rombocin 的特异性并提高其稳定性

IF 3 4区医学

Peptides Pub Date : 2024-01-12 DOI: 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>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 Lactococcus lactis. 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 Bacillus cereus 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.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"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}

引用次数: 0

Simplified drug efficacy evaluation system for vasopressin neurodegenerative disease using mouse disease-specific induced pluripotent stem cells 利用小鼠疾病特异性诱导多能干细胞简化血管加压素神经退行性疾病药物疗效评估系统。

IF 3 4区医学

Peptides Pub Date : 2024-01-11 DOI: 10.1016/j.peptides.2024.171151

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

{"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>Familial neurohypophyseal diabetes insipidus (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 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 induced pluripotent stem cells (iPSCs) from FNDI-model mice and differentiated vasopressin 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 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.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"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}

引用次数: 0

Structural modifications of INGAP-PP present in HTD4010 peptide potentiate its effect on rat islet gene expression and insulin secretion. HTD4010 肽中的 INGAP-PP 结构修饰增强了其对大鼠胰岛基因表达和胰岛素分泌的影响。

IF 3 4区医学

Peptides Pub Date : 2024-01-10 DOI: 10.1016/j.peptides.2024.171148

Macarena Algañarás, Carolina L. Román, Juan J. Gagliardino, Bárbara Maiztegui, Luis E. Flores

{"title":"Structural modifications of INGAP-PP present in HTD4010 peptide potentiate its effect on rat islet gene expression and insulin secretion.","authors":"Macarena Algañarás, Carolina L. Román, Juan J. Gagliardino, Bárbara Maiztegui, Luis E. Flores","doi":"10.1016/j.peptides.2024.171148","DOIUrl":"10.1016/j.peptides.2024.171148","url":null,"abstract":"<div>Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and altered insulin secretion due to a progressive loss of β-cell mass and function. Today, most antidiabetic agents are designed to resolve impaired insulin secretion and/or insulin resistance, and only GLP-1-based formulations contribute to stopping the decline in β-cell mass. HTD4010, a peptide carrying two modifications of the amino acid sequence of INGAP-PP (N-terminus acetylation and substitution of Asn13 by Ala) showed greater plasma stability and could be a good candidate for proposal as a drug that could improve β cell mass and function lost in T2D. In the present study, we showed that HTD4010 included in the culture media of normal rat islets at a dose 100 times lower than that used for INGAP-PP was able to modulate, in the same way as the original peptide, both insulin secretion in response to glucose and the expression of key genes related to insular function, insulin and leptin intracellular pathways, neogenesis, apoptosis, and inflammatory response. Our results confirm the positive effect of HTD4010 on β-cell function and gene expression of factors involved in the maintenance of β-cell mass. Although new assays in animal models of prediabetes and T2D must be performed to be conclusive, our results are very encouraging, and they suggest that the use of HTD4010 at a dose 100 times lower than that of INGAP-PP could minimize its side effects in a future clinical trial.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432921","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}

引用次数: 0

Intrathecal injections of angiotensin IV and oxytocin conjugates induce antihyperalgesia and antiallodynia in both sexes of rats 鞘内注射血管紧张素 IV 和催产素共轭物可诱导雌雄大鼠产生抗痛觉和抗镇痛作用

IF 3 4区医学

Peptides Pub Date : 2024-01-06 DOI: 10.1016/j.peptides.2024.171150

Lok-Hi Chow , Yuan-Hao Chen , Ying-Jie Chen , Hao-Yuan Hung , Pin-Chen Lin , Eagle Yi-Kung Huang

{"title":"Intrathecal injections of angiotensin IV and oxytocin conjugates induce antihyperalgesia and antiallodynia in both sexes of rats","authors":"Lok-Hi Chow , Yuan-Hao Chen , Ying-Jie Chen , Hao-Yuan Hung , Pin-Chen Lin , Eagle Yi-Kung Huang","doi":"10.1016/j.peptides.2024.171150","DOIUrl":"10.1016/j.peptides.2024.171150","url":null,"abstract":"<div>Our previous studies have established that intrathecal oxytocin (OT) and angiotensin IV (Ang IV) injections induce antihyperalgesia and antiallodynia in rodents. Ang IV, a renin-angiotensin system hexapeptide, acts as an endogenous inhibitor that inhibits the oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP). The pain inhibitory effects by Ang IV were found to be through its inhibition on IRAP to potentiate the effect of OT. However, these effects were found to be with a significant sex difference, which could be partially due to the higher expression of IRAP at the spinal cords of female. Therefore, we synthesized Ang IV and OT conjugates connected with a peptide bond and tested for their effects on hyperalgesia and allodynia. Carrageenan-induced hyperalgesia and partial sciatic nerve ligation (PSNL) were performed using rat models. Conjugates Ang IV-OT (Ang IV at the N-terminal) and OT-Ang IV (OT at the N-terminal) were synthesized and intrathecally injected into male and female rats. Our results showed that Ang IV-OT exhibited prominent antihyperalgesia in male rats, particularly during hyperalgesia recovery, whereas OT-Ang IV was more effective during development stage. Ang IV-OT showed clear antihyperalgesia in female rats, but OT-Ang IV had no significant effect. Notably, both conjugates alleviated neuropathic allodynia in male rats; however, OT-Ang IV had no effect in female rats, whereas Ang IV-OT induced significant antiallodynia. In conclusion, Ang IV-OT has greater therapeutic potential for treating hyperalgesia and allodynia than OT-Ang IV. Its effects were not affected by sex, unlike those of OT and OT-Ang IV, extending its possible clinical applications.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139394587","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}

引用次数: 0

Recent advances in peptide-based therapies for obesity and type 2 diabetes 基于肽的肥胖症和 2 型糖尿病疗法的最新进展。

IF 3 4区医学

Peptides Pub Date : 2024-01-05 DOI: 10.1016/j.peptides.2024.171149

Clifford J. Bailey , Peter R. Flatt , J. Michael Conlon

{"title":"Recent advances in peptide-based therapies for obesity and type 2 diabetes","authors":"Clifford J. Bailey , Peter R. Flatt , J. Michael Conlon","doi":"10.1016/j.peptides.2024.171149","DOIUrl":"10.1016/j.peptides.2024.171149","url":null,"abstract":"<div>Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by the results of several large clinical trials with incretin-based peptide therapies. Most of these studies have been conducted with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection and once daily tablet, and the once weekly injected dual agonist tirzepatide, which interacts with receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In individuals with T2DM these therapies have achieved reductions of glycated haemoglobin (HbA1c) by > 2% and lowered body weight by > 10%. In some studies, these agents tested in non-diabetic, obese individuals at much higher doses have lowered body weight by > 15%. Emerging evidence suggests these agents can also offer cardio-protective and potentially reno-protective effects. Other incretin-based peptide therapies in early clinical development, notably a triple GLP-1/GIP/glucagon receptor agonist (retatrutide) and a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), have shown strong efficacy. Although incretin therapies can incur adverse gastrointestinal effects these are for most patients mild-to-moderate and transient but result in cessation of treatment in some cases. Thus, the efficacy of new incretin-based peptide therapies is enhancing the opportunity to control body weight and blood glucose and improve the treatment of T2DM and obesity.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000020/pdfft?md5=05fca609d6a50eb0b28c9ea65fd7d0fa&pid=1-s2.0-S0196978124000020-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139111145","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}

引用次数: 0

An update on galanin and spexin and their potential for the treatment of type 2 diabetes and related metabolic disorders 关于加兰宁和沙棘苷及其治疗 2 型糖尿病和相关代谢紊乱的潜力的最新进展

IF 3 4区医学

Peptides Pub Date : 2024-01-01 DOI: 10.1016/j.peptides.2023.171096

Daniel M. Gallagher, Finbarr P.M. O’Harte, Nigel Irwin

{"title":"An update on galanin and spexin and their potential for the treatment of type 2 diabetes and related metabolic disorders","authors":"Daniel M. Gallagher, Finbarr P.M. O’Harte, Nigel Irwin","doi":"10.1016/j.peptides.2023.171096","DOIUrl":"10.1016/j.peptides.2023.171096","url":null,"abstract":"<div>Spexin (SPX) and galanin (GAL) are two neuropeptides widely expressed in the central nervous system as well as within peripheral tissues in humans and other species. SPX and GAL mediate their biological actions through binding and activation of galanin receptors (GALR), namely GALR1, GALR2 and GLAR3. GAL appears to trigger all three galanin receptors, whereas SPX interacts more specifically with GALR2 and GLAR3. Whilst the biological effects of GAL have been well-described over the years, in-depth knowledge of physiological action profile of SPX is still in its preliminary stages. However, it is recognised that both peptides play a significant role in modulating overall energy homeostasis, suggesting possible therapeutically exploitable benefits in diseases such as obesity and type 2 diabetes mellitus. Accordingly, although both peptides activate GALR’s, it appears GAL may be more useful for the treatment of eating disorders such as anorexia and bulimia, whereas SPX may find therapeutic application for obesity and obesity-driven forms of diabetes. This short narrative review aims to provide an up-to-date account of SPX and GAL biology together with putative approaches on exploiting these peptides for the treatment of metabolic disorders.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978123001614/pdfft?md5=9e168d2ec13c7b4856d79d4c8fe4a3c4&pid=1-s2.0-S0196978123001614-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10307041","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}

引用次数: 0

Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives 线粒体衍生肽：抗糖尿病功能和进化前景。

IF 3 4区医学

Peptides Pub Date : 2023-12-29 DOI: 10.1016/j.peptides.2023.171147

Satadeepa Kal , Sumana Mahata , Suborno Jati , Sushil K. Mahata

{"title":"Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives","authors":"Satadeepa Kal , Sumana Mahata , Suborno Jati , Sushil K. Mahata","doi":"10.1016/j.peptides.2023.171147","DOIUrl":"10.1016/j.peptides.2023.171147","url":null,"abstract":"<div>Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins encoded by short open-reading frames (sORF) in mitochondrial DNA (mtDNA). Currently, three types of MDPs have been identified: Humanin (HN), MOTS-c (Mitochondrial ORF within Twelve S rRNA type-c), and SHLP1–6 (small Humanin-like peptide, 1 to 6). The 12 S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, whereas HN and SHLP1–6 are encoded by the 16 S ribosomal RNA (MT-RNR2) gene. Special genetic codes are used in mtDNA as compared to nuclear DNA: (i) ATA and ATT are used as start codons in addition to the standard start codon ATG; (ii) AGA and AGG are used as stop codons instead of coding for arginine; (iii) the standard stop codon UGA is used to code for tryptophan. While HN, SHLP6, and MOTS-c are encoded by the H (heavy owing to high guanine + thymine base composition)-strand of the mtDNA, SHLP1–5 are encoded by the L (light owing to less guanine + thymine base composition)-strand. MDPs attenuate disease pathology including Type 1 diabetes (T1D), Type 2 diabetes (T2D), gestational diabetes, Alzheimer’s disease (AD), cardiovascular diseases, prostate cancer, and macular degeneration. The current review will focus on the MDP regulation of T2D, T1D, and gestational diabetes along with an emphasis on the evolutionary pressures for conservation of the amino acid sequences of MDPs.</div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074795","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}

引用次数: 0