| The dual roles of c-Jun NH2-terminal kinase signaling in Cr(VI)-induced apoptosis in JB6 cells. | |
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MedLine Citation:
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PMID: 21047991 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Occupational exposure to chromium (Cr) compounds has been shown to cause serious toxic and carcinogenic effects. The skin is an important target for the compounds in industrially exposed Cr workers. c-Jun NH(2)-terminal kinase (JNK) regulates cell proliferation, apoptosis, and differentiation. This protein's effects on cellular response depend upon the cell type and stimuli. The mechanisms by which hexavalent chromium (Cr(VI)) leads to apoptosis in the skin are unclear at present. The aim of this study is to examine whether JNK regulates apoptosis in Cr(VI)-exposed mouse JB6 epidermal cells. The present study showed that Cr(VI) induced apoptotic cell death through JNK activation. The blockage of JNK by small interference RNA (si-RNA) transfection suppressed Cr(VI)-induced apoptotic cell death with the concomitant downregulation of antiapoptotic Bcl-2 family proteins, mitochondrial membrane depolarization (Δψm), caspase activation, and poly (ADP-ribose) polymerase cleavage. However, inhibition of c-Jun expression by si-RNA transfection enhanced cytotoxicity, which corresponded to increasing apoptosis and Δψm. This phenomenon is associated with p53 activation caused by increasing reactive oxygen species (ROS) levels because of the downregulation of superoxide dismutase expression in si-c-Jun-transfected cells. Taken together, Cr(VI) induces apoptosis via JNK-mediated signaling, whereas c-Jun activation acts as an inhibitor of apoptotic signaling. Additionally, ROS generated by Cr(VI) is a pivotal regulator of JNK. |
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Authors:
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Young-Ok Son; John Andrew Hitron; Senping Cheng; Amit Budhraja; Zhuo Zhang; Nancy Lan Guo; Jeong-Chae Lee; Xianglin Shi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-03 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 119 ISSN: 1096-0929 ISO Abbreviation: Toxicol. Sci. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-20 Completed Date: 2011-06-02 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 335-45 Citation Subset: IM |
Affiliation:
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Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536-0305, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Blotting, Western Cell Line Chromium / toxicity* Electron Spin Resonance Spectroscopy JNK Mitogen-Activated Protein Kinases / metabolism* Mice Reactive Oxygen Species / metabolism Signal Transduction* Superoxides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1R01CA116697/CA/NCI NIH HHS; 1R01CA119028/CA/NCI NIH HHS; R01ES015375/ES/NIEHS NIH HHS; R01ES015518/ES/NIEHS NIH HHS; T32ES07266/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 11062-77-4/Superoxides; 7440-47-3/Chromium; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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