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Toxicol In Vitro. 2018 Oct 29;54:330-337. doi: 10.1016/j.tiv.2018.10.015. [Epub ahead of print]

Phosphorylation of eIF2α promotes cell survival in response to benzo[a]pyrene exposure.

Author information

1
Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, the Netherlands.
2
Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, the Netherlands. Electronic address: t.vandenbeucken@maastrichtuniversity.nl.

Abstract

Cellular adaptation is important to cope with various stresses induced by altered environmental conditions. By controlling mRNA translation rates cells may adapt to stress to promote survival. Phosphorylation of eIF2α at serine 51 is one of the pathways controlling mRNA translation. Here we investigated the role of phosphorylated eIF2α during exposure to the environmental carcinogen benzo(a)pyrene (BaP). For our study we used mouse embryonic fibroblasts with a wild type eIF2α (MEF WT) and mouse embryonic fibroblasts with an eIF2α S51A knock-in mutation that cannot be phosphorylated. Here, we show that eIF2α phosphorylation occurs in MEF WT cells but not in MEF S51A cells. Survival of MEF S51A cells is profoundly reduced compared to MEF WT controls after BaP exposure. No differences in DNA damage or ROS production were observed between MEF WT and S51A cells. Disruption of eIF2α phosphorylation caused increased levels of apoptosis in response to BaP. This work demonstrates that eIF2α phosphorylation is important for reducing apoptosis and promoting cell survival in order to adapt to BaP exposure.

KEYWORDS:

Apoptosis; Benzo[a]pyrene; eIF2α; mRNA translation

PMID:
30385349
DOI:
10.1016/j.tiv.2018.10.015
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