| Endothelin-1 aggravates hypoxia/reoxygenation-induced injury in renal epithelial cells through the activation of a Na+/Ca2+ exchanger. | |
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MedLine Citation:
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PMID: 15838349 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We analyzed the role of the Na/Ca2+ exchanger (NCX) in hypoxia/reoxygenation-induced injury and also its interaction with endothelin-1 in the proximal epithelial cell line LLC-PK1. The hypoxia/reoxygenation protocol caused a significant leakage of lactate dehydrogenase from parental LLC-PK1 cells, which was markedly suppressed by KB-R7943, a selective NCX inhibitor. Overexpression of wild-type NCX1 into LLC-PK1 cells enhanced the release of lactate dehydrogenase and produced more severe morphological changes, such as bleb formation, during reoxygenation. Endothelin-1 significantly aggravated hypoxia/reoxygenation- induced injuries in parental and NCX1-overexpressing LLC-PK1 cells. Such aggravation by endothelin-1 was not observed in cells overexpressing a deregulated NCX1 mutant, which displays no protein kinase C-dependent activation. KB-R7943 suppressed those cell injuries aggravated by endothelin-1, but not those in cells overexpressing a KB-R7943-insensitive NCX1 mutant. We confirmed that these cell injuries were relevant to their cellular Ca accumulations induced by hypoxia/reoxygenation. These results suggest that Ca2+ overload via NCX plays a critical role in hypoxia/reoxygenation-induced renal tubular injury, and that endothelin-1 aggravates the cell damage through the activation of NCX. |
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Authors:
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Takahiro Iwamoto; Satomi Kita; Takeshi Katsuragi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 44 Suppl 1 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2005-04-19 Completed Date: 2008-11-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: S462-6 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan. tiwamoto@cis.fukuoka-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Cell Hypoxia Cell Survival Dogs Dose-Response Relationship, Drug Endothelin-1 / metabolism* Epithelial Cells / drug effects, metabolism*, pathology Kidney / drug effects, metabolism*, pathology LLC-PK1 Cells Mutation Reperfusion Injury / metabolism*, pathology Sodium-Calcium Exchanger / antagonists & inhibitors, genetics, metabolism* Swine Thiourea / analogs & derivatives, pharmacology Transfection |
| Chemical | |
Reg. No./Substance:
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0/2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; 0/Endothelin-1; 0/Sodium-Calcium Exchanger; 0/sodium-calcium exchanger 1; 62-56-6/Thiourea; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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