title: Essential roles of p53 and MAPK cascades in microcystin-LR-induced germline apoptosis in Caenorhabditis elegans.
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 absolutely required for the apoptotic processes, and that the p53/CEP-1 and MAPKs cascades played essential roles in modulating MC-LR-induced germline apoptosis in C. elegans.
authors.affiliation: Department of Life Science, Huainan Normal University, Huainan 232001, China.
authors.forename: Shun-Chang
authors.initials: SC
authors.lastname: Wang
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Geng
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Tong
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D008387:Marine Toxins / Q000633:toxicity*; D052998:Microcystins / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D034501:Telomere-Binding Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; C112486:EGL-1 protein, C elegans; D008387:Marine Toxins; D052998:Microcystins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D034501:Telomere-Binding Proteins; D016159:Tumor Suppressor Protein p53; C438752:clk-2 protein, C elegans; D020928:Mitogen-Activated Protein Kinases; C057862:cyanoginosin LR