Nonylphenol induced apoptosis and autophagy involving the Akt/mTOR pathway in prepubertal Sprague-Dawley male rats in vivo and in vitro
Nonylphenol induced apoptosis and autophagy involving the Akt/mTOR pathway in prepubertal Sprague-Dawley male rats in vivo and in vitro
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壬基酚诱导青春期前 Sprague-Dawley 雄性大鼠体内和体外凋亡和自噬涉及 Akt/mTOR 通路
DOI：
10.1016/j.tox.2016.11.006
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发表时间：
2016-12-12
期刊：
影响因子：
4.5
通讯作者：
Yang, Kedi
中科院分区：
文献类型：
--
作者：
Huang, Wenting;Quan, Chao;Yang, Kedi
本研究探讨了壬基酚（NP）对青春期前雄性SD大鼠的体内和体外毒性作用。将42只3周龄大鼠随机分为6组，分别腹腔注射NP（0、NAC、25、50、100、100 + NAC mg/kg/2d，连续30 d）。NP诱导睾酮水平降低（25、50、100 mg/kg组分别为15.58%、17.23%、13.38%），引发与氧化应激相关的细胞凋亡，并干扰PI 3 K、PTEN、PDK 1、p-Akt、p-mTOR、p70 S6 K、caspase-3、LC 3B的mRNA和/或蛋白水平。NP引起附睾精子形态异常（50、100 mg/kg组分别为2.00、3.02倍）。NAC预处理可减轻NP诱导的ROS生成，恢复血清睾酮水平，改善对附睾精子的毒性作用。分离、纯化Sertoli细胞，用NP（0、10、20和30 μ M）处理12小时。NP干扰涉及PI 3 K/Akt/mTOR通路的caspase-3、切割-caspase-3、LC 3 B的mRNA和/或蛋白水平。它还降低了ABP、FSHR、N-钙粘蛋白、转铁蛋白、波形蛋白的蛋白水平;扰乱了除波形蛋白以外的所有基因水平。用渥曼青霉素预处理，减轻NP诱导的PI 3 K和PTEN蛋白水平的降低。总之，过量的NP暴露诱导细胞凋亡和自噬，导致体内和体外涉及PI 3 K/AKT/mTOR通路的生殖损伤。它还引发氧化应激和激素缺乏，降低精液质量。(C)2016爱思唯尔爱尔兰有限公司版权所有。
This research explores the detrimental effect of nonylphenol (NP) to prepubertal Sprague-Dawley male rats in vivo and in vitro. Herein, forty-two 3-week-old rats were randomly divided into six groups, which were treated with NP (0, NAC, 25, 50,100,100+NACmg/kg/2d for 30 consecutive days) by intraperitoneal injection. NP induced a reduction in testosterone (15.58%, 17.23%, 13.38% in 25, 50, 100 mg/kg group, respectively), triggered apoptosis related to oxidative stress, and disturbed mRNA and/or protein levels of PI3K, PTEN, PDK1, p-Akt, p-mTOR, p70S6K, caspase-3, LC3B. NP induced morphological abnormality in epididymal sperm (2.00-, 3.02-fold in 50, 100 mg/kg group, respectively). Pretreatment with NAC, attenuated NP-induced ROS production; recovered testosterone in serum, and ameliorated toxic effect in epididymal sperm. Sertoli cells were isolated, purified, treated with NP (0,10, 20, and 30 mu M) for 12 h. NP disturbed mRNA and/or protein levels of caspase-3, cleave-caspase-3, LC3 B involving the PI3K/Akt/mTOR pathway. It also decreased protein levels of ABP, FSHR, N-cadherin, transferrin, vimentin; disturbed the gene levels of all, but vimentin. Pretreatment with wortmannin, alleviated an NP-induced reduction in protein levels of PI3K and PTEN. In conclusion, excess NP exposure induces apoptosis and autophagy, causes reproductive lesions involving the PI3K/AKT/mTOR pathway both in vivo and in vitro. It also triggers oxidative stress and hormonal deficiency, reduces semen quality. (C) 2016 Elsevier Ireland Ltd. All rights reserved.