Document Detail

Linoleic acid prevents chloride influx and cellular lysis in rabbit renal proximal tubules exposed to mitochondrial toxicants.
MedLine Citation:
PMID:  11714247     Owner:  NLM     Status:  MEDLINE    
Despite many studies elucidating the mechanisms of necrotic cell death, the role of fatty acids released during necrosis remains to be determined. The goals of this study were to determine whether linoleic acid could protect rabbit renal proximal tubules (RPT) from necrotic cell death associated with mitochondrial dysfunction and oxidative injury and to determine the mechanisms involved. Exposure to antimycin A (10 microM) for 1 h or hypoxia (perfusion with 95% N(2)/5% CO(2)) for 1 or 2 h induced approximately 70% cellular lysis, as measured by lactate dehyrogenase release, versus 10% in controls. Preincubation with linoleic acid (100 microM) fully protected RPT from cellular lysis. RPT were also protected from lysis if linoleic acid was added 15 min after the addition of antimycin A. Measurements of free intracellular Ca(2+) concentrations showed that linoleic acid did not prevent the rise in intracellular Ca(2+) associated with a 30-min exposure to antimycin A. However, the influx of extracellular (36)Cl(-) following a 30-min exposure to antimycin A was ameliorated in the presence of linoleic acid. Linoleic acid did not prevent cellular lysis after exposure to hypoxia/reoxygenation (1 h/1 h) or t-butyl hydroperoxide (500 microM, 3 h). These data suggest that linoleic acid protects RPT during the late phase of cell death associated with inhibition of the electron transport chain but not oxidative injury. Several other fatty acids also protected RPT from lysis, and structure-activity relationship studies suggest that a free carboxyl terminus and at least one double bond are required for this action.
J H Moran; L A Mitchell; D F Grant
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  176     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-20     Completed Date:  2001-12-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-61     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
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MeSH Terms
Antimycin A / pharmacology
Calcium / metabolism
Cell Death / drug effects*
Chlorides / metabolism*
Electron Transport / drug effects
Fatty Acids / pharmacology
Kidney Tubules, Proximal / drug effects*,  metabolism,  pathology
L-Lactate Dehydrogenase / metabolism
Linoleic Acid / pharmacology*
Mitochondria / drug effects*
Grant Support
Reg. No./Substance:
0/Chlorides; 0/Fatty Acids; 2197-37-7/Linoleic Acid; 642-15-9/Antimycin A; 7440-70-2/Calcium; EC Dehydrogenase

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