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胰岛素样生长因子结合蛋白-5在甲基苯丙胺诱导的心肌细胞凋亡中的关键作用

Critical role of insulin‑like growth factor binding protein‑5 in methamphetamine‑induced apoptosis in cardiomyocytes.

作者信息

Leung Ka-Pui, Qu Yi-Hong, Qiao Dong-Fang, Xie Wei-Bing, Li Dong-Ri, Xu Jing-Tao, Wang Hui-Jun, Yue Xia

机构信息

Department of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Mol Med Rep. 2014 Nov;10(5):2306-12. doi: 10.3892/mmr.2014.2572. Epub 2014 Sep 16.

Abstract

Methamphetamine (MA) is a highly abused amphetamine‑like psychostimulant. At present, the mechanisms underlying MA‑induced cardiotoxicity are poorly understood. The cardiotoxic effects have yet not been clearly elucidated with respect to the apoptotic pathway. Insulin‑like growth factor binding protein‑5 (IGFBP5) is important for cell growth control and the induction of apoptosis. The aim of the present study was to analyze whether IGFBP5 is involved in MA‑induced apoptosis as a novel target. MA‑induced apoptosis was observed in neonatal rat ventricular myocytes (NRVMs) in a concentration‑dependent manner using a terminal deoxyribonucleotide transferase‑mediated dUTP nick end‑labeling assay. Using reverse transcription polymerase chain reaction and western blotting, MA was demonstrated to induce concentration‑dependent increases in the expression of IGFBP5. Silencing IGFBP5 with small interfering RNA significantly reduced apoptosis and suppressed the expression of caspase‑3 in NRVMs following treatment with MA. To the best of our knowledge, the present study provided the first evidence suggesting that IGFBP5 is a potential therapeutic target in MA‑induced apoptosis in vitro, providing a foundation for future in vivo studies.

摘要

甲基苯丙胺(MA)是一种被高度滥用的苯丙胺类精神兴奋剂。目前,MA诱导心脏毒性的潜在机制尚不清楚。关于凋亡途径,其心脏毒性作用尚未得到明确阐明。胰岛素样生长因子结合蛋白5(IGFBP5)对细胞生长控制和凋亡诱导很重要。本研究的目的是分析IGFBP5作为一个新靶点是否参与MA诱导的凋亡。使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法,在新生大鼠心室肌细胞(NRVMs)中观察到MA以浓度依赖性方式诱导凋亡。通过逆转录聚合酶链反应和蛋白质印迹法,证明MA可诱导IGFBP5表达呈浓度依赖性增加。用小干扰RNA沉默IGFBP5可显著减少MA处理后NRVMs中的凋亡,并抑制半胱天冬酶-3的表达。据我们所知,本研究首次提供证据表明IGFBP5是体外MA诱导凋亡的潜在治疗靶点,为未来的体内研究奠定了基础。

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