| Ceramide synthase is essential for endonuclease-mediated death of renal tubular epithelial cells induced by hypoxia-reoxygenation. | |
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MedLine Citation:
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PMID: 15479855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ceramide is known to play a role in the cell signaling pathway involved in apoptosis. Most studies suggest that enhanced ceramide generation is the result of hydrolysis of sphingomyelin by sphingomyelinases. However, the role of ceramide synthase in enhanced ceramide generation has not been previously examined in hypoxia-reoxygenation injury. In the present study, we demonstrated that 60-min hypoxia of rat renal tubular epithelial NRK-52E cells in a gas chamber with 95% N2-5% CO2 with glucose deprivation resulted in a significant increase in ceramide generation. The ceramide level further increased after reoxygenation for 60 min. Exposure of cells to hypoxia-reoxygenation resulted in a significant increase in ceramide synthase activity without any significant change in acid or neutral sphingomyelinase. The hypoxia-reoxygenation of NRK-52E cells was also associated with the release of endonuclease G (EndoG) from mitochondria to cytoplasm measured by Western blot analysis and endonuclease activity assay. It further led to the fragmentation of DNA and cell death. A specific inhibitor of ceramide synthase, fumonisin B1 (50 microM), suppressed hypoxia-reoxygenation-induced ceramide generation and provided protection against hypoxia-reoxygenation-induced EndoG release, DNA fragmentation, and cell death. Taken together, our data suggest that hypoxia-reoxygenation results in an activation of ceramide synthase rather than sphingomyelinase and that ceramide synthase-dependent ceramide generation is a key modulator of EndoG-mediated cytotoxicity in hypoxia-reoxygenation injury to renal tubular epithelial cells. |
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Authors:
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Alexei G Basnakian; Norishi Ueda; Xiaoman Hong; Valentin E Galitovsky; Xiaoyan Yin; Sudhir V Shah |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2004-10-12 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 288 ISSN: 1931-857X ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2005 Feb |
Date Detail:
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Created Date: 2005-01-07 Completed Date: 2005-02-09 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: F308-14 Citation Subset: IM |
Affiliation:
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University of Arkansas for Medical Sciences, LIttle Rock, Arkansas, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology* Cell Culture Techniques Cell Hypoxia DNA Damage Endodeoxyribonucleases / pharmacology* Epithelial Cells Kidney Tubules / cytology, pathology*, physiology* Oxidoreductases / pharmacology* Oxygen Rats Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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P01-D-58324-01A1//PHS HHS |
| Chemical | |
Reg. No./Substance:
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7782-44-7/Oxygen; EC 1.-/Oxidoreductases; EC 1.3.1.-/dihydroceramide desaturase; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.21.-/endonuclease G |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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