Curcumin: a potential therapeutic polyphenol, prevents noradrenaline-induced hypertrophy in rat cardiac myocytes

• Published in: Journal of pharmacy and pharmacology 2011-12, Vol.63 (12), p.1604-1612
• Main Authors: Ahuja, Suchit, Kohli, Shrey, Krishnan, Shruti, Dogra, Deepika, Sharma, Dinesh, Rani, Vibha
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Blotting, Western; cardiac hypertrophy; Cardiomegaly - chemically induced; Cardiomegaly - prevention & control; Cell Nucleus - drug effects; Cell Size - drug effects; Cell Survival; Cells, Cultured; curcumin; Curcumin - pharmacology; Cytosol - chemistry; Cytosol - metabolism; DNA - metabolism; Electrophoretic Mobility Shift Assay; GATA-4; GATA4 Transcription Factor - metabolism; Gene Expression - drug effects; Heart Ventricles - cytology; Immunohistochemistry; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - ultrastructure; noradrenaline; Norepinephrine - antagonists & inhibitors; Norepinephrine - toxicity; Rats; RNA - biosynthesis; RNA - genetics; therapeutics
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.2011.01363.x

Objectives  This study was designed to evaluate the effect of curcumin on H9c2 cardiac cell line and primary rat cardiac myocytes, using purified noradrenaline as a hypertrophy‐inducing agent. Methods  The concentration of curcumin at which cells were treated was determined by MTT (3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide) assay. The effect of this safe dose in preventing noradrenaline‐induced cardiac hypertrophy was assessed by biochemical analysis (estimating total protein content), molecular analysis (using RT‐PCR to study the expression of fetal genes like ANF), immunological analysis (by determining the nuclear localization of GATA‐4) and electrophoretic mobility shift assay (EMSA; to study DNA binding activity of GATA‐4). Key findings  Curcumin at a concentration of 8 µm was found to suppress the increase in cell size, protein content and enhanced marker gene expression (ANF) caused by noradrenaline. Immunocytochemistry and Western blot analysis showed that curcumin suppressed the localization of transcription factor GATA‐4 in the nucleus. It also showed a reduced DNA‐binding activity in the presence of noradrenaline as confirmed by EMSA. Conclusions  These findings suggest that curcumin reduces the hypertrophic marker gene expression by inhibiting nuclear localization and DNA binding activity of GATA‐4. Thus it has a great anti‐hypertrophic potential.