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

Abstract:

: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.

journal_name

Chem Res Toxicol

authors

Shi Q,Song X,Liu Z,Wang Y,Wang Y,Fu J,Su C,Xia X,Song E,Song Y

doi

10.1021/acs.chemrestox.6b00127

subject

Has Abstract

pub_date

2016-07-18 00:00:00

pages

1160-71

issue

7

eissn

0893-228X

issn

1520-5010

journal_volume

29

pub_type

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