title: [D-Lys3]-GHRP-6 exhibits pro-autophagic effects on skeletal muscle.
abstract: [D-Lys3]-GHRP-6 is regarded as a highly selective growth-hormone secretagogue receptor (GHSR) antagonist and has been widely used to investigate the dependency of GHSR-1a signalling mediated by acylated ghrelin. However, [D-Lys3]-GHRP-6 has been reported to influence other cellular processes which are unrelated to GHSR-1a. This study aimed to examine the effects of [D-Lys3]-GHRP-6 on autophagic and apoptotic cellular signalling in skeletal muscle. [D-Lys3]-GHRP-6 enhanced the autophagic signalling demonstrated by the increases in protein abundances of beclin-1 and LC3 II-to-LC3 1 ratio in both normal muscle and doxorubicin-injured muscle. [D-Lys3]-GHRP-6 reduced the activation of muscle apoptosis induced by doxorubicin. No histological abnormalities were observed in the [D-Lys3]-GHRP-6-treated muscle. Intriguingly, the doxorubicin-induced increase in centronucleated muscle fibres was not observed in muscle treated with [D-Lys3]-GHRP-6, suggesting the myoprotective effects of [D-Lys3]-GHRP-6 against doxorubicin injury. The [D-Lys3]-GHRP-6-induced activation of autophagy was found to be abolished by the co-treatment of CXCR4 antagonist, suggesting that the pro-autophagic effects of [D-Lys3]-GHRP-6 might be mediated through CXCR4. In conclusion, [D-Lys3]-GHRP-6 exhibits pro-autophagic effects on skeletal muscle under both normal and doxorubicin-injured conditions.
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Angus P
authors.initials: AP
authors.lastname: Yu
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Xiao M
authors.initials: XM
authors.lastname: Pei
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Sin
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Shea P
authors.initials: SP
authors.lastname: Yip
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Benjamin Y
authors.initials: BY
authors.lastname: Yung
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Chan
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Cesar S
authors.initials: CS
authors.lastname: Wong
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. Electronic address: parco.siu@polyu.edu.hk.
authors.forename: Parco M
authors.initials: PM
authors.lastname: Siu
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D001596:Benzylamines; D000080027:Cyclams; D004317:Doxorubicin / Q000009:adverse effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage*; D010880:Piperidines / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology; D019718:Receptors, CXCR4; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000577:Amides; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D001596:Benzylamines; D000080027:Cyclams; C520836:GHRP-6, Lys(3)-; D006571:Heterocyclic Compounds; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D009842:Oligopeptides; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; D052999:Quinazolinones; D019718:Receptors, CXCR4; C524424:YIL 781; D004317:Doxorubicin; C119369:TAK 779; C088327:plerixafor
keywords: Apoptosis; Autophagy; CXCR4; GHSR antagonist; Ghrelin; Skeletal myofibre