| Caspase-dependent and -independent pathways for cadmium-induced apoptosis in cultured kidney proximal tubule cells. | |
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MedLine Citation:
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PMID: 16597613 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The nephrotoxic metal cadmium at micromolar concentrations induces apoptosis of rat kidney proximal tubule (PT) cells within 3-6 h of exposure. The underlying cell death pathways remain poorly defined. Using Hoechst 33342/ethidium bromide nuclear staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell death assays, 10-50 microM cadmium induced apoptosis of immortalized rat kidney cells derived from the S1-segment of PT at 6 and 24 h, but necrosis at 24 h only. Cadmium (10-50 microM) also caused mitochondrial cytochrome c (cyt. c)- and apoptosis-inducing factor release at 24 h, but not at 6 h, as measured by immunofluorescence imaging and immunoblotting. Caspases-9 and -3 were activated only by 10 microM cadmium for 24 h, and accordingly apoptosis was significantly reduced by the respective inhibitors (z-LEHD-fmk, z-DEVD-fmk; 10 microg/ml) at 24 h, but not at 6 h, without affecting necrosis. At 6 h, 10 microM cadmium increased the activity of the calcium-activated protease calpain, but not at 24 h, and calpain inhibitors (ALLN, PD 150606; 10-30 microM) blocked apoptosis by 10 microM cadmium at 3-6 h. However, PD-150606 also attenuated caspase-3 activity and apoptosis at 24 h, suggesting calpain-dependent caspase activation. Thus cadmium-induced apoptosis of PT cells involves a complex and sensitive interplay of signaling cascades involving mitochondrial proapoptotic factors, calpains and caspases, whose activation is also determined by cadmium concentration and the duration of cadmium exposure. |
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Authors:
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Wing-Kee Lee; Marouan Abouhamed; Frank Thévenod |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-04-04 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 291 ISSN: 1931-857X ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-06 Completed Date: 2006-10-26 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F823-32 Citation Subset: IM |
Affiliation:
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Department of Physiology and Pathophysiology, Faculty of Medicine, University of Witten/Herdecke, Witten, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acrylates
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pharmacology Animals Apoptosis / drug effects* Cadmium / toxicity* Caspases / metabolism* Cell Line Cells, Cultured Cytochromes c / metabolism Kidney Tubules, Proximal / cytology*, drug effects, physiology Rats |
| Chemical | |
Reg. No./Substance:
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0/Acrylates; 0/PD 150606; 7440-43-9/Cadmium; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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