Document Detail

Attenuation of oxidant-mediated endothelial cell injury with docosahexaenoic acid: the role of intracellular iron.
MedLine Citation:
PMID:  9774176     Owner:  NLM     Status:  MEDLINE    
Previous studies have demonstrated that altering the fatty acid composition of porcine pulmonary artery endothelial cells (PAEC) significantly modulates their susceptibility to oxidative stimuli, e.g. H2O2. Based on observations that fatty acids also function to transport iron, an important catalyst for H2O2-mediated hydroxyl radical generation, we hypothesized that fatty acid-induced alterations in PAEC iron metabolism contribute to modulation of PAEC oxidant susceptibility. To test this hypothesis, PAEC were treated with culture medium supplemented with 0.1 mM oleic (18:1), linolenic (18:3) or docosahexaenoic (22:6) acids or with an equivalent volume of ethanol vehicle for 3 h. After thorough washing and incubation in unsupplemented culture medium for 24 h, PAEC monolayers were subjected to additional studies. Supplementation with 22:6 attenuated lactate dehydrogenase (LDH) release from PAEC 2 h following treatment with 100 microM H2O2 for 30 min (% LDH release: ETOH-control = 7.9 +/- 1.6, 22:6-control = 5.9 +/- 0.9, ETOH-H2O2 = 26.4 +/- 4.2, 22:6-H2O2* = 16.2 +/- 2.9; *P < 0.05 vs ETOH-H2O2). In a non-cellular system, 18:1 and 18:3 were more effective than their methyl ester derivatives or 22:6 at translocating iron from aqueous to hydrophobic environments. In contrast, only supplementation with 22:6 significantly increased PAEC uptake of 57Fe and human umbilical vein endothelial cell (HUVEC) ferritin content, whereas none of the supplementation conditions altered PAEC catalytic iron measured with bleomycin. These novel observations indicate that specific fatty acids are capable of altering PAEC iron uptake and ferritin content thereby contributing to the understanding of the mechanisms by which fatty acids modulate the oxidant susceptibility of vascular endothelial cells.
M D Ober; C M Hart
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Prostaglandins, leukotrienes, and essential fatty acids     Volume:  59     ISSN:  0952-3278     ISO Abbreviation:  Prostaglandins Leukot. Essent. Fatty Acids     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-12-09     Completed Date:  1998-12-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8802730     Medline TA:  Prostaglandins Leukot Essent Fatty Acids     Country:  SCOTLAND    
Other Details:
Languages:  eng     Pagination:  127-35     Citation Subset:  IM    
Department of Medicine, Indiana University and Richard L. Roudebush Veterans Affairs Medical Centers, Indianapolis, USA.
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MeSH Terms
Bleomycin / pharmacology
Cell Survival / drug effects
Cell-Free System
Cells, Cultured
Chelating Agents / pharmacology
Deferoxamine / pharmacology
Docosahexaenoic Acids / pharmacology*
Endothelium, Vascular / cytology*,  drug effects,  metabolism
Ferritins / metabolism
Hydrogen Peroxide / toxicity
Iron / metabolism*
L-Lactate Dehydrogenase / metabolism
Linoleic Acid / pharmacology
Oleic Acid / pharmacology
Oxidants / toxicity*
Pulmonary Artery
Umbilical Veins
Reg. No./Substance:
0/Chelating Agents; 0/Oxidants; 11056-06-7/Bleomycin; 112-80-1/Oleic Acid; 2197-37-7/Linoleic Acid; 25167-62-8/Docosahexaenoic Acids; 70-51-9/Deferoxamine; 7439-89-6/Iron; 7722-84-1/Hydrogen Peroxide; 9007-73-2/Ferritins; EC Dehydrogenase

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

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