4-[1-Ethyl-1-methylhexy]-phenol induces apoptosis and interrupts Ca2+ homeostasis via ROS pathway in Sertoli TM4 cells.

Xiaozhen Liu,Gaoyi Peng,Mingyong Xie,Danfei Huang,Zhaoliang Zhu,Fuxiang Li

doi:10.1007/s11356-021-17041-0

Abstract

Biological effect of an individual nonylphenol (NP) isomer extremely relies upon the side chain structure. This research was designed to evaluate the impact of NP isomer, 4-[1-ethyl-1-methylhexy]-phenol (NP65), on Sertoli cells in vitro. Sertoli TM4 cells were exposed to various concentration (0, 0.1, 1, 10, or 20μM) of NP65 for 24h, and the outcomes indicated that treatment of NP65 induced reactive oxygen species (ROS) generation, oxidative stress, and apoptosis for Sertoli TM4 cells. In addition, it was found that NP65 exposure affected homeostasis of Ca2+ in Sertoli TM4 cells by increasing cytoplasm [Ca2+]i, inhibiting Ca2+-ATPase activity and decreasingcyclic adenosine monophosphate (cAMP) concentration. Pretreatment with ROS scavenger, N-acetylcysteine (NAC), attenuated NP65-induced oxidative stress as well as apoptosis for TM4 cells. Furthermore, NAC blocked NP65-induced disorders of Ca2+ homeostasis by attenuating the growth of intracellular [Ca2+]i and the inhibition of Ca2+-ATPase and cAMP activities. Thus, we have demonstrated that NP65 induced apoptosis as well as acted as a potent inhibitor of Ca2+-ATPase activity and resulted in disorder of Ca2+ homeostasis in Sertoli TM4 cells; ROS participated in the process. Our results supported the view that oxidative stress acted an essential role within the development of apoptosis and Ca2+ overload in TM4 cells as a consequence of NP65 stimulation.

Highlights

Nonylphenols (NPs), the major degraded products of nonylphenol polyethoxylate (NPEOs), were thought to be one of the endocrine disrupting chemicals (EDCs), which could interrupt the endocrine system function of human and animal
Pretreatment of NAC mitigated the decline of superoxide dismutase (SOD) activity and the growth of malnoic dialdehyde (MDA) content induced by NP65
We proposed that NP65 induced lipid peroxidation in TM4 cells, which resulted in oxidative stress in NP65 treated TM4 cells

Summary

Introduction

Nonylphenols (NPs), the major degraded products of nonylphenol polyethoxylate (NPEOs), were thought to be one of the endocrine disrupting chemicals (EDCs), which could interrupt the endocrine system function of human and animal. Studies have demonstrated that NPs was seriously threatening reproductive health (Malmir et al 2020), immune function (Xia et al 2013) and system of nerves (Li et al 2019) in human and animals. The existence of NPs within the environment has become a growing worry because they have been shown to be estrogenic compounds in addition to the persistence and toxicity, while most of the studies were focused on industrial nonylphenol, which mostly include a combination of para-substituted mono-alkylphenols containing numerous branched and isomeric nonyl groups. As far as we know, there have been few studies to observe the toxicity of NPs from the perspective of isomers specificity, while the mechanism on toxicity of NP isomers has been barely studied

Methods

Results

Conclusion