Document Detail

Trimetazidine increases phospholipid turnover in ventricular myocyte.
MedLine Citation:
PMID:  9350047     Owner:  NLM     Status:  MEDLINE    
Trimetazidine (TMZ) is an anti-ischemic compound devoid of hemodynamic effects. It was recently suggested to induce cardiomyocyte protection by a mechanism involving lipid metabolism. The effects of TMZ were evaluated in rats on cardiac lipid composition, and in cultured rat cardiomyocytes on phospholipid metabolism. Rats were treated with TMZ for 4 weeks, and the fatty acid compositions were determined. Treatment with TMZ induced a significant decrease in phospholipid linoleic acid, balanced by a small increase in oleic and stearic acids. These changes were not correlated to alterations in plasma fatty acid composition. Cultured ventricular myocytes were treated with TMZ, 16 and 1 before experimentation. The time-dependent incorporation of radio labelled precursors of membrane phospholipids (3-inositol, 14C-ethanolamine, 14C-choline, 14C-arachidonic acid, 10 mumol/L) was investigated. The cells were harvested 30, 60, 105 or 150 min after precursor addition. In TMZ-cells, arachidonic acid (AA) incorporation was increased in the phospholipids, but not in other lipid fractions. This increase elicited a net increase in the total AA uptake. The incorporation of 3-inositol in the phospholipids was strongly stimulated by TMZ, although the uptake of inositol was not altered. The difference was significant within 30 min, and after 150 min the phospholipid labelling in TMZ cells was higher by 70%. A similar result was obtained with ethanolamine as precursor, which turnover increased by 50% in TMZ-treated cells. Conversely, the incorporation of choline was not significantly affected by the presence of TMZ. In conclusion TMZ appears to interfere with the metabolism of phospholipids in cardiac myocytes in a manner which could indicate an increase of membrane phospholipid turnover.
E Sentex; J P Sergiel; A Lucien; A Grynberg
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  175     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-12-04     Completed Date:  1997-12-04     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  153-62     Citation Subset:  IM    
I.N.R.A., Unité de Nutrition Lipidique, Dijon, France.
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MeSH Terms
Arachidonic Acids / metabolism,  pharmacology
Carbon Radioisotopes / diagnostic use
Cells, Cultured
Chromatography, Thin Layer
Ethanolamine / metabolism,  pharmacology
Fatty Acids / metabolism
Heart Ventricles / cytology,  drug effects*,  metabolism
Inositol / metabolism,  pharmacology
Phospholipids / metabolism*
Rats, Wistar
Scintillation Counting
Trimetazidine / pharmacology*
Vasodilator Agents / pharmacology*
Reg. No./Substance:
0/Arachidonic Acids; 0/Carbon Radioisotopes; 0/Fatty Acids; 0/Phospholipids; 0/Vasodilator Agents; 141-43-5/Ethanolamine; 5011-34-7/Trimetazidine; 6917-35-7/Inositol

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