Change in post-translational modifications of histone H3, heat-shock protein-27 and MAP kinase p38 expression by curcumin in streptozotocin-induced type I diabetic nephropathy

Br J Pharmacol. 2008 Mar;153(6):1225-31. doi: 10.1038/sj.bjp.0707666. Epub 2008 Jan 21.

Abstract

Background and purpose: Curcumin has been used to treat cancer, diabetes and other pathologies. However, little is known regarding its role in altering post-translational modifications of histone H3. A recent report suggests that acute hyperglycaemia induces a global down-regulation of gene expression in human tissues and epigenetic regulation of gene expression could be a novel mechanism underlying the pathological processes of hyperglycaemia. The present study was undertaken to examine changes in histone modification by curcumin treatment which prevents development of type I diabetic nephropathy.

Experimental approach: Male Sprague-Dawley rats were rendered diabetic using a single dose of streptozotocin (55 mg kg(-1), i.p.). Diabetic nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Post-translational modifications of histone H3, heat shock protein-27 (HSP-27) and mitogen-activated protein (MAP) kinase p38 expression were examined by western blotting.

Key results: Treatment of diabetic rats with curcumin significantly decreased blood urea nitrogen and creatinine and increased albumin; variables associated with the development of diabetic nephropathy. There were also increased levels of HSP-27 and MAP kinase (p38) in diabetic kidney. However, curcumin treatment prevented this increase in HSP-27 and p38 expression. Moreover, at nuclear level curcumin prevented the decrease in dephosphorylation and increases acetylation of histone H3.

Conclusions and implications: Our results suggested that protection against development of diabetic nephropathy by curcumin treatment involved changes in post-translational modifications of histone H3, expression of HSP-27 and MAP kinase p38 in diabetic kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Curcumin / pharmacology*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Type 1 / complications
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Gene Expression Regulation / drug effects*
  • Heat-Shock Proteins / drug effects
  • Heat-Shock Proteins / metabolism
  • Histones / drug effects
  • Histones / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • p38 Mitogen-Activated Protein Kinases / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • Heat-Shock Proteins
  • Histones
  • Streptozocin
  • p38 Mitogen-Activated Protein Kinases
  • Curcumin