Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin via the PPARγ/Akt/NO signaling pathway
Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin via the PPARγ/Akt/NO signaling pathway
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DOI：
10.1016/j.diabres.2015.02.012
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发表时间：
2015-05-01
影响因子：
5.1
通讯作者：
Jiang, Qingsong
中科院分区：
文献类型：
--
作者：
Chen, Rongchun;Peng, Xiaofeng;Jiang, Qingsong
目的：探讨姜黄素对糖尿病大鼠心肌细胞肥大的影响及其参与PPAR-γ/Akt/NO信号通路的可能机制。方法：采用高糖(25.5 mmol/L)和胰岛素(0.1mU/L)诱导的心肌细胞肥大及姜黄素的抗心肌肥大作用，通过测定细胞表面积、蛋白含量和心钠素基因表达来评价姜黄素的抗心肌肥大作用。结果：HGI诱导的心肌细胞肥大以ANF mRNA表达、总蛋白含量和细胞表面积增加为特征，PPAR-γ和Akt的mRNA和蛋白表达均下调，与enos mRNA表达、eNOS含量和NO浓度下降相平行。姜黄素(1、3、10mU/L)呈浓度依赖性抑制HGI的作用。选择性PPARγ拮抗剂GW9662(10MU/L)可阻断姜黄素的作用。AKT阻断剂LY294002(20MU/L)和一氧化氮合酶抑制剂N-G-硝基-L-精氨酸甲酯(100MU/L)也可减弱姜黄素的作用。结论：姜黄素可通过激活PPAR-γ/AKT/NO信号通路改善HGI诱导的心肌细胞肥大。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Aim: To investigate the potential effect of curcumin on cardiomyocyte hypertrophy and a possible mechanism involving the PPAR gamma/Akt/NO signaling pathway in diabetes.Methods: The cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L) and insulin (0.1 mu mol/L) (HGI) and the antihypertrophic effect of curcumin were evaluated in primary culture by measuring the cell surface area, protein content and atrial natriuretic factor (ANF) mRNA expression. The mRNA and protein expressions were assayed by reverse transcription PCR and Western blotting, whereas the NO concentration and endothelial NO synthase (eNOS) activity were determined using nitrate reduction and ELISA methods, respectively.Results: The cardiomyocyte hypertrophy induced by HGI was characterized by increasing ANF mRNA expression, total protein content, and cell surface area, with downregulated mRNA and protein expressions of both PPAR gamma and Akt, which paralleled the declining eNOS mRNA expression, eNOS content, and NO concentration. The effects of HGI were inhibited by curcumin (1, 3, 10 mu mol/L) in a concentration-dependent manner. GW9662 (10 mu mol/L), a selective PPAR gamma antagonist, could abolish the effects of curcumin. LY294002 (20 mu mol/L), an Akt blocker, and N-G-nitro-L-arginine-methyl ester (100 mu mol/L), a NOS inhibitor, could also diminish the effects of curcumin.Conclusions: The results suggested that curcumin supplementation can improve HGI-induced cardiomyocytes hypertrophy in vitro through the activation of PPAR gamma/Akt/NO signaling pathway. (C) 2015 Elsevier Ireland Ltd. All rights reserved.