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

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

DOI:
10.3892/mmr.2014.2572
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发表时间:
2014-11
影响因子:
3.4
通讯作者:
Yue X
Yue X
中科院分区:
医学4区
文献类型:
--
作者:
Leung KP;Qu YH;Qiao DF;Xie WB;Li DR;Xu JT;Wang HJ;Yue X

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甲基苯丙胺 (MA) 是一种高度滥用的类似苯丙胺的精神兴奋剂。目前,MA 引起的心脏毒性的机制尚不清楚。与细胞凋亡途径有关的心脏毒性作用尚未明确阐明。胰岛素样生长因子结合蛋白 5 (IGFBP5) 对于细胞生长控制和诱导细胞凋亡非常重要。本研究的目的是分析IGFBP5是否作为新靶标参与MA诱导的细胞凋亡。使用末端脱氧核糖核苷酸转移酶介导的 dUTP 缺口末端标记测定,以浓度依赖性方式在新生大鼠心室肌细胞 (NRVM) 中观察到 MA 诱导的细胞凋亡。使用逆转录聚合酶链反应和蛋白质印迹,MA 被证明可诱导 IGFBP5 表达浓度依赖性增加。 MA 治疗后,用小干扰 RNA 沉默 IGFBP5 可显着减少细胞凋亡并抑制 NRVM 中 caspase-3 的表达。据我们所知,本研究提供了第一个证据表明IGFBP5是MA诱导的体外细胞凋亡的潜在治疗靶点,为未来的体内研究奠定了基础。
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.
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