Liu Xiaozhen, Nie Shaoping, Huang Danfei, Xie Mingyong
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
Environ Toxicol Pharmacol. 2015 Mar;39(2):815-24. doi: 10.1016/j.etap.2015.02.004. Epub 2015 Feb 16.
Nonylphenol (NP) is considered an important environmental toxicant, which may disrupt male reproductive system. The aim of this study was to investigate 4-n-nonylphenol (4-n-NP) induced apoptosis and its related mechanism in mouse Sertoli cell line, TM4 cells. Our results showed that NP treatment (0.1, 1, 10, 20 and 30 μM) decreased cell viability and induced apoptosis in the cells, accompanied by alteration of Bcl-2 family mRNA expression, activation of caspases-3, release of Ca(2+), and increase of reactive oxygen species (ROS) generation. Subsequently, it was found that the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in the cells were markedly decreased, and maleic dialdehyde (MDA) content was increased by NP treatment. Then activation of the mitogen-activated protein kinases (MAPKs) pathways and inhibition of Akt pathway were simultaneously detected in NP challenged TM4 cells. Taken together, it was concluded that NP induced cytotoxicity and apoptosis in TM4 cells, and the apoptosis may be mediated via MAPKs and Akt pathways in addition to Ca(2+) release and ROS generation.
壬基酚(NP)被认为是一种重要的环境毒物,可能会扰乱雄性生殖系统。本研究的目的是探讨4-正壬基酚(4-n-NP)诱导小鼠支持细胞系TM4细胞凋亡及其相关机制。我们的结果表明,NP处理(0.1、1、10、20和30μM)降低了细胞活力并诱导细胞凋亡,同时伴随着Bcl-2家族mRNA表达的改变、半胱天冬酶-3的激活、Ca(2+)的释放以及活性氧(ROS)生成的增加。随后,发现细胞中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-PX)的水平显著降低,而NP处理使丙二醛(MDA)含量增加。然后在NP刺激的TM4细胞中同时检测到丝裂原活化蛋白激酶(MAPKs)途径的激活和Akt途径的抑制。综上所述,得出结论:NP诱导TM4细胞的细胞毒性和凋亡,除了Ca(2+)释放和ROS生成外,凋亡可能还通过MAPKs和Akt途径介导。