[D-Lys3]-GHRP-6 exhibits pro-autophagic effects on skeletal muscle

Angus P. Yu, Xiao M. Pei, Thomas K. Sin, Shea Ping Yip, Yat Ming Yung, Wing Chi Chan, Sze Chuen Cesar Wong, Parco M. Siu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

5 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume401
DOIs
Publication statusPublished - 5 Feb 2015

Keywords

  • Apoptosis
  • Autophagy
  • CXCR4
  • Ghrelin
  • GHSR antagonist
  • Skeletal myofibre

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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