High oligomycin concentrations augment 6-keto-PGF1 alpha production in ventricular cardiomyocytes.
Incubation of cultured ventricular cardiomyocytes with high oligomycin concentrations (100 micrograms/ml), either alone or combined with 2-deoxyglucose (20 mM), led to the rapid depletion of cellular ATP. Inositol (poly)phosphate production decreased, and 6-keto PGF1 alpha production was increased. In cells depleted of ATP, either by low oligomycin concentrations or by sodium azide, 6-keto PGF1 alpha was not appreciably increased. There was a 25% rise in the release of fatty acids from the sn-2 position in glycerophospholipids. We suggest that oligomycin at high concentrations causes the release of free arachidonic acid from phospholipids either by non-PIP2-specific PLC and DG lipase or by phospholipase D, phosphatidic acid phosphatase and DG lipase. The effect is unrelated to decreased cellular ATP content.
Pinson
A
A
Laboratory of Myocardial Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Zilberman
Y
Y
Tirosh
R
R
Trembovler
V
V
Shohami
E
E
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology*; D051381:Rats
D007295:Inositol Phosphates; D009840:Oligomycins; D015121:6-Ketoprostaglandin F1 alpha; D000255:Adenosine Triphosphate; D003847:Deoxyglucose