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Toxicol Lett. 2019 May 15;306:25-34. doi: 10.1016/j.toxlet.2019.02.002. Epub 2019 Feb 8.

Polychlorinated biphenyl quinone-induced signaling transition from autophagy to apoptosis is regulated by HMGB1 and p53 in human hepatoma HepG2 cells.

Author information

1
Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China.
2
Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China. Electronic address: songyangwenrong@hotmail.com.

Abstract

Autophagy, which works to remove stress and maintain cellular homeostasis, is usually considered a "pro-survival" signal. Contrarily, apoptosis is programmed "pro-death" machinery. Polychlorinated biphenyls (PCBs) are a group of ubiquitous industrial pollutants. Our previous studies illustrated that a PCB quinone metabolite, PCB29-pQ, elicited both autophagy and apoptosis. However, the signaling underlying the autophagy and apoptosis cross-talk has not been characterized. Here, we found that PCB29-pQ-induced autophagy mainly occurred at a lower concentration (5 μM), while apoptosis mostly arose at a higher concentration (15 μM) in HepG2 cells. Next, we demonstrated the elevation of intracellular calcium levels and calpain activity with PCB29-pQ treatment; however, the unaffected subcellular location of truncated ATG5 and Beclin1 suggested the irrelevance of calpain towards the autophagy-to-apoptosis signaling shift. HMGB1 and p53 both serve as transcription factors that play crucial roles in the regulation of PCB29-pQ-induced autophagy and apoptosis. PCB29-pQ not only enhanced the expression of HMGB1 and p53 but also promoted their binding and cytosolic translocation. Interestingly, HMGB1 rather than p53 plays a primary role in 5 μM of PCB29-pQ-induced autophagy in the nucleus; however, p53 promoted apoptosis to a great extent in the cytosol at the dose of 15 μM PCB29-pQ. Together, HMGB1 and p53 provided a subtle balance between autophagy and apoptosis, thus determining the fate of PCB29-pQ-treated cells.

KEYWORDS:

Apoptosis; Autophagy; HMGB1; PCBs; p53

PMID:
30742880
DOI:
10.1016/j.toxlet.2019.02.002
[Indexed for MEDLINE]

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