Melatonin-induced autophagy is associated with degradation of MyoD protein in C2C12 myoblast cells

Chi Hyun Kim, Kyunghwan Kim, Yeong Min Yoo

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

MyoD is a muscle-specific transcriptional factor that acts as a master switch for skeletal muscle differentiation. This protein regulates myoblast proliferation and myogenic differentiation and is also a short-lived regulatory protein that is degraded by the ubiquitin system. However, the lysosomal pathway of MyoD protein degradation remains unknown. In this study, we sought to determine whether melatonin (1, 2 mm)-induced autophagy causes the degradation of MyoD protein in C2C12 myoblast cells. Melatonin induced a significant increase in expression of the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 proteins in a dose-dependent manner. Melatonin treatment also significantly increased p-ERK, Ras, and p-Akt expressions in a dose-dependent manner. However, Bax expression was high compared with the absence of melatonin treatment, and Bcl-2 expression was high in the 0.1-0.5 mm melatonin treatments and low in the 1 and 2 mm melatonin treatments. Under the same conditions, cytosolic MyoD protein was significantly decreased in a dose-dependent manner and completely eliminated by 36 hr. This decrease in MyoD protein involved ubiquitin-mediated proteasomal activity with proteasome inhibitor MG132 or autophagy-dependent lysosomal degradation with lysosomal inhibitor bafilomycin A1 (Baf-A1). In the same condition, phosphorylation of the mammalian target of rapamycin, p-mTOR, and p-S6K expression with Baf-A1 or Baf-A1-plus melatonin treatment were significantly decreased compared with the levels after treatment with melatonin only. Together, these results suggest that melatonin (1, 2 mm)-induced autophagy results in partial lysosomal degradation of MyoD protein in C2C12 myoblast cells.

Original languageEnglish
Pages (from-to)289-297
Number of pages9
JournalJournal of Pineal Research
Volume53
Issue number3
DOIs
Publication statusPublished - 2012 Oct 1

All Science Journal Classification (ASJC) codes

  • Endocrinology

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