Document Detail


Modulation by Gly, Ca, and acidosis of injury-associated unesterified fatty acid accumulation in proximal tubule cells.
MedLine Citation:
PMID:  7840236     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have examined the dependence of unesterified fatty acid accumulation by intact, freshly isolated proximal tubules on Ca2+, pH, and the cytoprotective amino acid, glycine, during injury induced by hypoxia, antimycin, or antimycin plus ionomycin. In the absence of glycine, similarly high levels of fatty acid accumulation were seen during all three injury conditions irrespective of whether tubules were incubated in normal 1.25 mM Ca2+ medium or in medium where Ca2+ was buffered to 0.1 microM, a maneuver which prevented injury-associated increase of cytosolic-free Ca2+ as measured with fura 2. In the presence of glycine, which strongly suppressed development of lethal membrane damage for at least 60 min and did not have any apparent direct effects on fatty acid accumulation, both Ca(2+)-independent and Ca(2+)-dependent components of fatty acid accumulation were discernible. The Ca(2+)-independent component accounted for approximately 2/3 of fatty acid accumulation and did not vary as Ca2+ ranged from 10 nM to 1 microM. Unequivocal Ca(2+)-dependent accumulation occurred when Ca2+ exceeded 10 microM. Lowering pH to 6.9 had a moderate, generalized suppressive effect on fatty acid accumulation, including the major Ca(2+)-independent component, irrespective of the presence of glycine. These data emphasize the role of Ca(2+)-independent fatty acid accumulation during proximal tubule cell injury, clarify the modulatory actions of the potent, intrinsic cytoprotective factors, glycine and reduced pH, and provide insight into the relationship between fatty acid accumulation and lethal membrane damage.
Authors:
J M Weinberg; M A Venkatachalam; H Goldberg; N F Roeser; J A Davis
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  The American journal of physiology     Volume:  268     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1995 Jan 
Date Detail:
Created Date:  1995-02-27     Completed Date:  1995-02-27     Revised Date:  2013-02-11    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  F110-21     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Michigan, Ann Arbor.
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MeSH Terms
Descriptor/Qualifier:
Acidosis / metabolism
Animals
Antimycin A / analogs & derivatives,  toxicity
Biological Transport / drug effects
Calcium / pharmacology*
Cell Hypoxia
Dose-Response Relationship, Drug
Drug Interactions
Egtazic Acid / pharmacology
Fatty Acids, Nonesterified / metabolism*
Glycine / pharmacology*
Hydrogen-Ion Concentration
Ionomycin / toxicity
Kidney Cortex / drug effects,  metabolism*,  pathology
Kidney Tubules, Proximal / drug effects,  metabolism*,  pathology
Kinetics
L-Lactate Dehydrogenase / analysis
Male
Phospholipids / metabolism*
Rabbits
Time Factors
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Phospholipids; 11118-72-2/antimycin; 56-40-6/Glycine; 56092-81-0/Ionomycin; 642-15-9/Antimycin A; 67-42-5/Egtazic Acid; 7440-70-2/Calcium; EC 1.1.1.27/L-Lactate Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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