Essential roles of p53 and MAPK cascades in microcystin-LR-induced germline apoptosis in Caenorhabditis elegans

Environmental Science & Technology
Shunchang WangHan-Qing Yu

Abstract

Hepatotoxin microcystin-LR (MC-LR) can induce apoptosis in a variety of cells. However, the underlying pathways of MC-LR-induced apoptosis have not been well elucidated yet. To find out the roles of underlying pathways in apoptosis signaling in response to MC-LR, germ cell corpses were scored in Caenorhabditis elegans N2 wild type and strains carrying mutated alleles homologous to their mammalian counterparts. We found that exposure to MC-LR at 1.0 μg/L significantly increased germline apoptosis in N2. Germline apoptosis was absent at all doses in ced-3 and ced-4 loss-of-function strains. MC-LR-induced apoptosis was blocked in Bcl-2 gain-of-function strain ced-9(n1950), whereas it showed a slight increase in BH3-only protein EGL-1 mutated strain. The null mutation of cep-1, which is the homologue of p53 tumor suppressor gene, significantly inhibited MC-LR-induced cell death, and checkpoint proteins HUS-1 and CLK-2 exerted proapoptotic effects. Apoptosis in loss-of-function members of ERK, JNK, and p38 MAPK signaling pathways reduced significantly under MC-LR exposure, and members of MAPKK subgroup JKK-1, MEK-1, and SEK-1 worked cooperatively. Our results show that the caspase protein CED-3 and Apaf-1 protein CED-4 were absolute...Continue Reading

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Jun 25, 2013·Environmental Science & Technology·Wei TengDongyuan Zhao
Sep 25, 2015·International Journal of Molecular Sciences·Yunhui LiYuepu Pu
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Feb 22, 2014·Aquatic Toxicology·Cheng ZengGuangyu Li
Apr 4, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xinyue YouYang Luan

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