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Sci Rep. 2017 Jul 19;7(1):5916. doi: 10.1038/s41598-017-06067-5.

Methylglyoxal and Advanced Glycation End products: Insight of the regulatory machinery affecting the myogenic program and of its modulation by natural compounds.

Author information

1
Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
2
Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia.
3
Department of Biomedical Science, Catholic University of Daegu, Gyeongsan, 38430, Republic of Korea.
4
Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu, 41062, Republic of Korea.
5
Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541, Republic of Korea. gorapadoc0315@hanmail.net.
6
Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541, Republic of Korea. inhochoi@ynu.ac.kr.

Abstract

Methylglyoxal (MG) is a reactive dicarbonyl intermediate and a precursor of advanced glycation end products (AGEs). The authors investigated the role played by AGEs in muscle myopathy and the amelioration of its effects by curcumin and gingerol. In addition to producing phenotypical changes, MG increased oxidative stress and reduced myotube formation in C2C12 cells. RAGE (receptor for AGEs) expression was up-regulated and MYOD and myogenin (MYOG) expressions were concomitantly down-regulated in MG-treated cells. Interestingly, AGE levels were higher in plasma (~32 fold) and muscle (~26 fold) of diabetic mice than in control mice. RAGE knock-down (RAGEkd) reduced the expressions of MYOD and MYOG and myotube formation in C2C12 cells. In silico studies of interactions between curcumin or gingerol and myostatin (MSTN; an inhibitor of myogenesis) and their observed affinities for activin receptor type IIB (ACVRIIB) suggested curcumin and gingerol reduce the interaction between MSTN and ACVRIIB. The findings of this study suggest enhanced AGE production and subsequent RAGE-AGE interaction obstruct the muscle development program, and that curcumin and gingerol attenuate the effect of AGEs on myoblasts.

PMID:
28725008
PMCID:
PMC5517486
DOI:
10.1038/s41598-017-06067-5
[Indexed for MEDLINE]
Free PMC Article

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