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The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans.
Chemosphere. 2014 Aug; 108:231-8.C

Abstract

The induction of apoptosis is recognized to be a major mechanism of tributyltin (TBT) toxicity. However, the underlying signaling pathways for TBT-induced apoptosis remain unclear. In this study, using the nematode Caenorhabditis elegans, we examined whether DNA damage response (DDR) pathway and mitogen-activated protein kinase (MAPK) signaling cascades are involved in TBT-induced germline apoptosis and cell cycle arrest. Our results demonstrated that exposing worms to TBT at the dose of 10nM for 6h significantly increased germline apoptosis in N2 strain. Germline apoptosis was absent in strains that carried ced-3 or ced-4 loss-of-function alleles, indicating that both caspase protein CED-3 and Apaf-1 protein CED-4 were required for TBT-induced apoptosis. TBT-induced apoptosis was blocked in the Bcl-2 gain-of-function strain ced-9(n1950), whereas TBT induced a minor increase in the BH3-only protein EGL-1 mutated strain egl-1(n1084n3082). Checkpoint proteins HUS-1 and CLK-2 exerted proapoptotic effects, and the null mutation of cep-1, the homologue of tumor suppressor gene p53, significantly inhibited TBT-induced apoptosis. Apoptosis in the loss-of-function strains of ERK, JNK and p38 MAPK signaling pathways were completely or mildly suppressed under TBT stress. These results were supported by the results of mRNA expression levels of corresponding genes. The present study indicated that TBT-induced apoptosis required the core apoptotic machinery, and that DDR genes and MAPK pathways played essential roles in signaling the processes.

Authors+Show Affiliations

Department of Life Sciences, Huainan Normal University, Huainan, Anhui 232001, PR China. Electronic address: yunwang2001@163.com.Department of Life Sciences, Huainan Normal University, Huainan, Anhui 232001, PR China.Department of Life Sciences, Huainan Normal University, Huainan, Anhui 232001, PR China.Department of Life Sciences, Huainan Normal University, Huainan, Anhui 232001, PR China.Department of Life Sciences, Huainan Normal University, Huainan, Anhui 232001, PR China.Department of Life Sciences, Huainan Normal University, Huainan, Anhui 232001, PR China.Department of Life Sciences, Huainan Normal University, Huainan, Anhui 232001, PR China.

Pub Type(s)

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

Language

eng

PubMed ID

24534158

Citation

Wang, Yun, et al. "The Roles of DNA Damage-dependent Signals and MAPK Cascades in Tributyltin-induced Germline Apoptosis in Caenorhabditis Elegans." Chemosphere, vol. 108, 2014, pp. 231-8.
Wang Y, Wang S, Luo X, et al. The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans. Chemosphere. 2014;108:231-8.
Wang, Y., Wang, S., Luo, X., Yang, Y., Jian, F., Wang, X., & Xie, L. (2014). The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans. Chemosphere, 108, 231-8. https://doi.org/10.1016/j.chemosphere.2014.01.045
Wang Y, et al. The Roles of DNA Damage-dependent Signals and MAPK Cascades in Tributyltin-induced Germline Apoptosis in Caenorhabditis Elegans. Chemosphere. 2014;108:231-8. PubMed PMID: 24534158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans. AU - Wang,Yun, AU - Wang,Shunchang, AU - Luo,Xun, AU - Yang,Yanan, AU - Jian,Fenglei, AU - Wang,Xuemin, AU - Xie,Lucheng, Y1 - 2014/02/15/ PY - 2013/09/18/received PY - 2013/12/23/revised PY - 2014/01/11/accepted PY - 2014/2/19/entrez PY - 2014/2/19/pubmed PY - 2014/10/23/medline KW - Apoptosis KW - Caenorhabditis elegans KW - DNA damage response KW - MAPK KW - Tributyltin SP - 231 EP - 8 JF - Chemosphere JO - Chemosphere VL - 108 N2 - The induction of apoptosis is recognized to be a major mechanism of tributyltin (TBT) toxicity. However, the underlying signaling pathways for TBT-induced apoptosis remain unclear. In this study, using the nematode Caenorhabditis elegans, we examined whether DNA damage response (DDR) pathway and mitogen-activated protein kinase (MAPK) signaling cascades are involved in TBT-induced germline apoptosis and cell cycle arrest. Our results demonstrated that exposing worms to TBT at the dose of 10nM for 6h significantly increased germline apoptosis in N2 strain. Germline apoptosis was absent in strains that carried ced-3 or ced-4 loss-of-function alleles, indicating that both caspase protein CED-3 and Apaf-1 protein CED-4 were required for TBT-induced apoptosis. TBT-induced apoptosis was blocked in the Bcl-2 gain-of-function strain ced-9(n1950), whereas TBT induced a minor increase in the BH3-only protein EGL-1 mutated strain egl-1(n1084n3082). Checkpoint proteins HUS-1 and CLK-2 exerted proapoptotic effects, and the null mutation of cep-1, the homologue of tumor suppressor gene p53, significantly inhibited TBT-induced apoptosis. Apoptosis in the loss-of-function strains of ERK, JNK and p38 MAPK signaling pathways were completely or mildly suppressed under TBT stress. These results were supported by the results of mRNA expression levels of corresponding genes. The present study indicated that TBT-induced apoptosis required the core apoptotic machinery, and that DDR genes and MAPK pathways played essential roles in signaling the processes. SN - 1879-1298 UR - https://www.unboundmedicine.com/medline/citation/24534158/The_roles_of_DNA_damage_dependent_signals_and_MAPK_cascades_in_tributyltin_induced_germline_apoptosis_in_Caenorhabditis_elegans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-6535(14)00111-8 DB - PRIME DP - Unbound Medicine ER -