Exogenous oxidants initiate hydrolysis of endothelial cell inositol phospholipids

D. Michael  Shasby; Mark Yorek; Sandra S Shasby

doi:10.1182/blood.V72.2.491.491

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Exogenous oxidants initiate hydrolysis of endothelial cell inositol phospholipids

Journal article

Open access

Peer reviewed

Exogenous oxidants initiate hydrolysis of endothelial cell inositol phospholipids

D. Michael Shasby, Mark Yorek and Sandra S Shasby

Blood, Vol.72(2), pp.491-499

08/1988

DOI: 10.1182/blood.V72.2.491.491

PMID: 2840985

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https://doi.org/10.1182/blood.V72.2.491.491View

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Abstract

Oxidants released from inflammatory cells contribute to the pathogenesis of acute inflammatory edema in many models. Chemically produced oxidants can reversibly alter the barrier properties of cultured endothelial and epithelial monolayers. This report examines the effects of nonlytic doses of H2O2 on endothelial cell lipids. H2O2 oxidized omega-6 fatty acids in the endothelial cells and initiated hydrolysis of endothelial cell phospholipids. When endothelial cells were exposed to peroxidized linoleic acid, it caused lysis of the cells at doses 1,000-fold lower than effective doses of H2O2. The phospholipid hydrolysis was directed primarily at the inositol phospholipids and consisted of both A and C type phospholipase activity. The phospholipase A hydrolysis resulted in increases in endothelial cell free fatty acids and lysophosphatidylinositol. The phospholipase C hydrolysis resulted in increases in diglycerides, phosphatidic acid, and inositol polyphosphate levels. The phospholipase C hydrolysis of phosphatidylinositol is known to activate protein kinase C in most cells. Stimulation of protein kinase C with phorbol-12,13-dibutyrate increased albumin flux across endothelial monolayers and altered endothelial cell shape, similar to effects of oxidants. These data are consistent with the hypothesis that oxidant-initiated hydrolysis of endothelial cell inositol phospholipids contributes to oxidant-mediated reversible changes in endothelial monolayer barrier function.

Hydrolysis

Animals

Calcium - physiology

Oxidation-Reduction

Endothelium, Vascular - metabolism

Swine

Cells, Cultured

Hydrogen Peroxide - pharmacology

L-Lactate Dehydrogenase - analysis

Phorbol Esters - pharmacology

Phosphatidylinositols - metabolism

Fatty Acids - metabolism

Details

Title: Subtitle: Exogenous oxidants initiate hydrolysis of endothelial cell inositol phospholipids
Creators: D. Michael Shasby - Department of Internal Medicine, University of Iowa Hospitals, Iowa City 52242
Mark Yorek
Sandra S Shasby
Resource Type: Journal article
Publication Details: Blood, Vol.72(2), pp.491-499
DOI: 10.1182/blood.V72.2.491.491
PMID: 2840985
NLM abbreviation: Blood
ISSN: 0006-4971
eISSN: 1528-0020
Grant note: HL14230 / NHLBI NIH HHS HL33540 / NHLBI NIH HHS HL36605 / NHLBI NIH HHS
Language: English
Date published: 08/1988
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094584802771

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