title: Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy.
abstract: A detrimental consequence of hypermethylation is hyperhomocysteinemia (HHcy), that causes oxidative stress, inflammation, and matrix degradation, which leads to multi-pathology in different organs. Although, it is well known that hypermethylation leads to overall gene silencing and hypomethylation leads to overall gene activation, the role of such process in skeletal muscle dysfunction during HHcy condition is unclear. In this study, we emphasized the multiple mechanisms including epigenetic alteration by which HHcy causes skeletal muscle myopathy. This review also highlights possible role of methylation, histone modification, and RNA interference in skeletal muscle dysfunction during HHcy condition and potential therapeutic molecules, putative challenges, and methodologies to deal with HHcy mediated skeletal muscle dysfunction. We also highlighted that B vitamins (mainly B12 and B6), with folic acid supplementation, could be useful as an adjuvant therapy to reverse these consequences associated with this HHcy conditions in skeletal muscle. However, we would recommend to further study involving long-term trials could help to assess efficacy of the use of these therapeutic agents. J. Cell. Biochem. 118: 2108-2117, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, Kentucky, 40202.|Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky, 40202.
authors.forename: Avisek
authors.initials: A
authors.lastname: Majumder
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky, 40202.
authors.forename: Jyotirmaya
authors.initials: J
authors.lastname: Behera
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky, 40202.
authors.forename: Nevena
authors.initials: N
authors.lastname: Jeremic
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, Kentucky, 40202.|Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky, 40202.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic; D005492:Folic Acid / Q000008:administration & dosage; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D034622:RNA Interference; D045162:Thiazolidinediones / Q000627:therapeutic use; D014805:Vitamin B 12 / Q000008:administration & dosage*; D025101:Vitamin B 6 / Q000008:administration & dosage*
chemical_list: D006657:Histones; D045162:Thiazolidinediones; D006710:Homocysteine; D025101:Vitamin B 6; D008687:Metformin; D005492:Folic Acid; D014805:Vitamin B 12
keywords: ECM REMODELING; HOMOCYSTEINE; HYPERMETHYLATION; MUSCLE DYSFUNCTION; OXIDATIVE STRESS