Involvement of ROS-mediated Mitochondrial Dysfunction and SIRT3 Down-regulation in Tris(2-chloroethyl)phosphate-induced Cell Cycle Arrest

Overview

Journal Toxicol Res (Camb)

Publisher Oxford University Press

Date 2018 Aug 10

PMID 30090360

Citations 5

Authors

Wenjuan Zhang

Youjian Zhang

Tian Xu

Zhiyuan Wang

Jing Wang

Wei Xiong

Wenhong Lu

Hongyan Zheng

Jing Yuan

Affiliations

Soon will be listed here.

Abstract

Tris(2-chloroethyl)phosphate (TCEP) is a flame retardant in plastics. It is bio-accumulative and persistent in the environment and has been detected in ambient and indoor air, surface and groundwater, food, house dust, and consumer products. Studies showed that TCEP can cause damage to the liver and kidneys of rats. However, the mechanisms underlying TCEP remain unclear. To investigate the effect of TCEP on mitochondrial function and cell fate, Chang liver cells were treated with TCEP (3.12, 12.50, 50.00, and 200.00 mg L) for 24 and 48 h. The results showed that TCEP increased mitochondrial reactive oxygen species production, disrupted mitochondrial integrity and caused mitochondrial dysfunction, representing increased intercellular free Ca levels, decreased mitochondrial membrane potential and mitochondrial DNA copies as well as reduced ATP synthesis, and G2/M cell cycle arrest with down-regulation of SIRT3, forkhead box O3a and manganese superoxide dismutase proteins. The findings suggest that TCEP caused cell cycle arrest through down-regulation of SIRT3 is involved in mitochondrial oxidative stress.

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