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Essential roles of p53 and MAPK cascades in microcystin-LR-induced germline apoptosis in Caenorhabditis elegans.
Environ Sci Technol. 2012 Mar 20; 46(6):3442-8.ES

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Wang SC
Department of Life Science, Huainan Normal University, Huainan 232001, China.
Geng ZZ
No affiliation info available
Wang Y
No affiliation info available
Tong ZH
No affiliation info available
Yu HQ
No affiliation info available

MeSH

AnimalsApoptosisBacterial ToxinsCaenorhabditis elegansCaenorhabditis elegans ProteinsMarine ToxinsMicrocystinsMitogen-Activated Protein KinasesProto-Oncogene Proteins c-bcl-2RNA InterferenceRepressor ProteinsSignal TransductionTelomere-Binding ProteinsTumor Suppressor Protein p53

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22353034

Citation

Wang, Shun-Chang, et al. "Essential Roles of P53 and MAPK Cascades in microcystin-LR-induced Germline Apoptosis in Caenorhabditis Elegans." Environmental Science & Technology, vol. 46, no. 6, 2012, pp. 3442-8.
Wang SC, Geng ZZ, Wang Y, et al. Essential roles of p53 and MAPK cascades in microcystin-LR-induced germline apoptosis in Caenorhabditis elegans. Environ Sci Technol. 2012;46(6):3442-8.
Wang, S. C., Geng, Z. Z., Wang, Y., Tong, Z. H., & Yu, H. Q. (2012). Essential roles of p53 and MAPK cascades in microcystin-LR-induced germline apoptosis in Caenorhabditis elegans. Environmental Science & Technology, 46(6), 3442-8. https://doi.org/10.1021/es203675y
Wang SC, et al. Essential Roles of P53 and MAPK Cascades in microcystin-LR-induced Germline Apoptosis in Caenorhabditis Elegans. Environ Sci Technol. 2012 Mar 20;46(6):3442-8. PubMed PMID: 22353034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Essential roles of p53 and MAPK cascades in microcystin-LR-induced germline apoptosis in Caenorhabditis elegans. AU - Wang,Shun-Chang, AU - Geng,Zhi-Zhong, AU - Wang,Yun, AU - Tong,Zhong-Hua, AU - Yu,Han-Qing, Y1 - 2012/03/07/ PY - 2012/2/23/entrez PY - 2012/2/23/pubmed PY - 2012/9/14/medline SP - 3442 EP - 8 JF - Environmental science & technology JO - Environ Sci Technol VL - 46 IS - 6 N2 - 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. SN - 1520-5851 UR - https://www.unboundmedicine.com/medline/citation/22353034/Essential_roles_of_p53_and_MAPK_cascades_in_microcystin_LR_induced_germline_apoptosis_in_Caenorhabditis_elegans_ L2 - https://doi.org/10.1021/es203675y DB - PRIME DP - Unbound Medicine ER -