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

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 incr...

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Published in:	Scientific reports Vol. 7; no. 1; pp. 5916 - 10
Main Authors:	Baig, Mohammad Hassan, Jan, Arif Tasleem, Rabbani, Gulam, Ahmad, Khurshid, Ashraf, Jalaluddin M., Kim, Taeyeon, Min, Han Sol, Lee, Yong Ho, Cho, Won-Kyung, Ma, Jin Yeul, Lee, Eun Ju, Choi, Inho
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 19-07-2017 Nature Publishing Group Nature Portfolio
Subjects:	13 13/100 14/63 631/114/2397 631/80/304 64/60 82 Activin Advanced glycosylation end products Age Animals Biological Products - pharmacology Catechols - pharmacology Cell Differentiation - drug effects Cell Line Computer Simulation Curcumin Curcumin - pharmacology Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Fatty Alcohols - pharmacology Gene expression Gene Expression Regulation Gene Knockdown Techniques Glucose Glycation End Products, Advanced - metabolism Glycosylation Humanities and Social Sciences Hyperglycemia Insulin Mice, Inbred C57BL multidisciplinary Muscle Development - drug effects Myoblasts MyoD protein Myogenesis Myogenin Myopathy Myostatin Myostatin - pharmacology Oxidative stress Plasma Proteins Pyruvaldehyde Pyruvaldehyde - metabolism Receptor for Advanced Glycation End Products - genetics Receptor for Advanced Glycation End Products - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Science Science (multidisciplinary) Transcription factors
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Summary:	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 (RAGE kd ) 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-017-06067-5