Quinones Derived from Polychlorinated Biphenyls Induce ROS-Dependent Autophagy by Evoking an Autophagic Flux and Inhibition of mTOR/p70S6k

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• 作者：Qiong Shi ; Xiufang Song ; Zixuan Liu ; Yawen Wang ; Yuxin Wang ; Juanli Fu ; Chuanyang Su ; Xiaomin Xia ; Erqun Song ; Yang Song
• 刊名：Chemical Research in Toxicology
• 出版年：2016
• 出版时间：July 18, 2016
• 年：2016
• 卷：29
• 期：7
• 页码：1160-1171
• 全文大小：884K
• 年卷期：0
• ISSN：1520-5010

文摘

Autophagy is a “self-eating” destructive process that eliminates damaged organelles to maintain cellular homeostasis. Polychlorinated biphenyls (PCBs) are one of the most infamous industrial pollutants, which are ubiquitous in nature. In the present study, we found that an active, quinone-type PCB metabolite (PCB29-pQ) treatment causes an autophagic response through mTOR/p70S6k inhibition in HepG2 and MDA-MB-231 cells. Furthermore, our data suggested that PCB29-pQ enhances autophagosome formation through autophagic vacuole (AV) biogenesis, which evokes autophagic flux and induces AV–lysosome colocalization. The inhibition of autophagy enhanced PCB29-pQ-caused cytotoxicity, suggesting that autophagy serves as pro-survival machinery that plays a protective role in the early stage of PCB29-pQ-induced insult. However, higher concentration of PCB29-pQ exposure (>5 μM) caused autophagic cell death, which implied a shift from “pro-survival” to “pro-death” upon autophagic signaling. N-Acetylcysteine suppressed PCB29-pQ-induced autophagy and cytotoxicity, suggesting that ROS plays an important role in the regulation of PCB29-pQ-induced autophagy. Because autophagy shows significant implications in various human diseases and conditions, our current study provides a new mechanism for PCB-associated toxicity.