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邻苯二甲酸二(2-乙基己基)酯通过线粒体途径诱导 GC-2spd 细胞凋亡。

Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells.

机构信息

Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People's Republic of China.

Department of Non-communicable chronic disease prevention and control, Wuhan Centers for Disease Prevention and Control, 24 Jianghan N.Road, Wuhan, 430015, People's Republic of China.

出版信息

Environ Toxicol. 2017 Mar;32(3):1055-1064. doi: 10.1002/tox.22304. Epub 2016 Jul 14.

Abstract

Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 μM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 μM) and glutathione peroxidase (GSH-Px) activity (50 and 100 μM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1055-1064, 2017.

摘要

邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种合成聚合物的增塑剂,是一种众所周知的内分泌干扰化学物质(EDC)和生殖毒物。为了阐明 DEHP 诱导生殖功能障碍的机制尚不明确,本研究使用 GC-2spd 细胞来研究 DEHP 诱导雄性生殖系统毒性的相关分子机制。结果表明,细胞凋亡的死亡明显诱导 DEHP 暴露超过 100μM。此外,DEHP 处理可诱导 GC-2spd 细胞中的氧化应激,涉及超氧化物歧化酶(SOD)活性(200μM)和谷胱甘肽过氧化物酶(GSH-Px)活性(50 和 100μM)的降低。此外,DEHP 诱导还导致 Bax/Bcl-2 比值升高,细胞色素 c 释放以及 procaspase-3 和 procaspase-9 的分解。综上所述,我们的工作提供了证据,表明 DEHP 暴露可能通过氧化应激介导的线粒体途径诱导 GC-2spd 细胞凋亡。©2016 年 Wiley 期刊,环境毒理学 32:1055-1064,2017。

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