Insulin induced alteration in post-translational modifications of histone H3 under hyperglycemic condition in L6 skeletal muscle myoblasts

Dhiraj G. Kabra (1) , Jeena Gupta (1) , Kulbhushan Tikoo (1)

1 NIPER - National Institute of Pharmaceutical Education and Research

Chromatin remodelling events, especially histone modifications are proposed to form the mainstay for most of the biological processes. However, the role of these histone modifications in the progression of diabetes is still unknown. Hyperglycemia plays a major role in diabetes and its complications. Present study was undertaken to check the effect of insulin on alterations in post-translational modifications of histone H3 in L6 myoblasts under hyperglycemic condition. We provide first evidence that insulin under hyperglycemic condition alters multiple histone modifications by enhanced production of reactive oxygen species. Insulin induces dose dependant changes in Lysine 4 and 9 methylation, Ser 10 phosphorylation and acetylation of histone H3. Interestingly, insulin induced generation of reactive oxygen species induces dephosphorylation and deacetylation of histone H3. Preincubation with catalase and DPI prevents these changes in posttranslational modifications of histone H3. Furthermore, changes in histone H3 phosphorylation was found to be independent of ERK, p38, RSK2 and MSK1. Moreover, serine/threonine phosphatase inhibitor, okadaic acid attenuates insulin induced dephosphorylation and deacetylation of histone H3, suggesting role of serine/threonine phosphatases in altering modifications of histone H3. These changes in epigenetic modifications can provide new insights into pathogenesis of diabetes.

Mots clés: Cat; CM-DCF-DA; DPI; ERK; HAT; HDAC; MAPK; NOX; MSK1; PP2A; PP1; ROS; RSK2; Insulin; hyperglycemia; L6 skeletal muscle; histone modification; oxidative stress; and Serine/threonine phosphatase

Dhiraj G. Kabra, Jeena Gupta, Kulbhushan Tikoo. Insulin induced alteration in post-translational modifications of histone H3 under hyperglycemic condition in L6 skeletal muscle myoblasts. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1792 (6), pp.574. ⟨10.1016/j.bbadis.2009.03.003⟩. ⟨hal-00562902⟩