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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
Author(s) -
Tikoo K,
Meena R L,
Kabra D G,
Gaikwad A B
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707666
Subject(s) - diabetic nephropathy , curcumin , blood urea nitrogen , p38 mitogen activated protein kinases , histone , histone h3 , medicine , streptozotocin , endocrinology , creatinine , nephropathy , protein kinase a , heat shock protein , kidney , kinase , pharmacology , diabetes mellitus , biology , biochemistry , gene
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. British Journal of Pharmacology (2008) 153 , 1225–1231; doi: 10.1038/sj.bjp.0707666 ; published online 21 January 2008