Lysophosphatidylcholine accumulation in cardiomyocytes requires
thrombin activation of ca2+-independent pla2.
McHowat, Jane, and Michael H. Creer.
Department of Pathology, University of Arkansas for Medical
Sciences, Little Rock, Arkansas, 72205
APStracts 3:0505H, 1996.
Lysophosphatidylcholine (LPC) accumulates during ischemia or following
thrombin stimulation of cardiac myocytes. We determined whether LPC
accumulation reflects increased LPC production via PLA2 activation,
inhibition of LPC catabolism or a combination of both. Thrombin
-stimulated normoxic myocytes demonstrated a 1.5-fold increase in LPC
content and a 2 to 2.5-fold increase in membrane-associated, calcium
-independent PLA2 activity. Despite PLA2 activation, hypoxia alone did
not increase LPC content. Thrombin-stimulated hypoxic myocytes
demonstrated a 2.5-fold increase in LPC content with no further
increase in PLA2 activity. Inhibition of calcium-independent PLA2
prevented the thrombin-induced increase in both PLA2 activity and LPC
content under normoxic and hypoxic conditions. Pharmacologic blockade
of the hypoxia-induced inhibition of LPC catabolism did not affect
hypoxia or thrombin-induced PLA2 activation or normoxic, thrombin
-induced LPC accumulation but greatly diminished the magnitude of LPC
accumulation following thrombin stimulation of hypoxic myocytes.
Thus, accumulation of LPC during ischemia or following thrombin
stimulation is absolutely dependent on PLA2 activation and further
augmented by inhibition of LPC catabolism.
Received 5 September 1996; accepted in final form 6 November
1996.
APS Manuscript Number H793-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996