Document Detail


Selective hydrolysis of plasmalogen phospholipids by Ca2+-independent PLA2 in hypoxic ventricular myocytes.
MedLine Citation:
PMID:  9611139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Accelerated phospholipid catabolism occurs early after the onset of myocardial ischemia and is likely to be mediated by the activation of one or more phospholipases in ischemic tissue. We hypothesized that hypoxia increases phospholipase A2 (PLA2) activity in isolated ventricular myocytes, resulting in increased lysophospholipid and arachidonic acid production, contributing to arrhythmogenesis in ischemic heart disease. The majority of ventricular myocyte arachidonic acid was found in plasmalogen phospholipids. Hypoxia increased membrane-associated, Ca2+-independent, plasmalogen-selective PLA2 activity, resulting in increased arachidonic acid release and lysoplasmenylcholine production. Pretreatment with the specific Ca2+-independent PLA2 inhibitor bromoenol lactone blocked hypoxia-induced increases in PLA2 activity, arachidonic acid release, and lysoplasmenylcholine production. Lysoplasmenylcholine produced action potential derangements, including shortening of action potential duration, and induced early and delayed afterdepolarizations in normoxic myocytes. The electrophysiological alterations induced by lysoplasmenylcholine would likely contribute to the initiation of arrhythmogenesis in the ischemic heart.
Authors:
J McHowat; S Liu; M H Creer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  274     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-08-06     Completed Date:  1998-08-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  C1727-37     Citation Subset:  IM    
Affiliation:
Department of Pathology, St. Louis University Medical School, St. Louis, Missouri 63104, USA.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Adenosine Triphosphate / metabolism,  pharmacology
Animals
Arachidonic Acid / metabolism
Calcium / pharmacology
Cell Hypoxia*
Cell Membrane / enzymology
Female
Heart Ventricles / enzymology
Hydrolysis
Kinetics
Lysophospholipids / metabolism,  pharmacology
Myocardium / enzymology*,  ultrastructure
Naphthalenes / pharmacology
Phosphodiesterase Inhibitors / pharmacology
Phospholipases A / metabolism*
Phospholipases A2
Phospholipids / analysis,  metabolism*
Plasmalogens / metabolism*
Pyrones / pharmacology
Rabbits
Chemical
Reg. No./Substance:
0/Lysophospholipids; 0/Naphthalenes; 0/Phosphodiesterase Inhibitors; 0/Phospholipids; 0/Plasmalogens; 0/Pyrones; 0/lysoplasmalogens; 506-32-1/Arachidonic Acid; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; 88070-98-8/6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2

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


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