Preconditioning cultured human pediatric myocytes requires adenosine and protein kinase c. Ikonomidis, John S., Toshizumi Shirai, Richard D. Weisel, Bogdan Derylo, Vivek Rao, Catherine I. Whiteside, Donald A. G. Mickle, Ren -Ke Li. The Division of Cardiovascular Surgery, the Department of Clinical Biochemistry and the Centre for Cardiovascular Research, The Toronto Hospital and the University of Toronto, Toronto, Ontario, Canada
APStracts 3:0442H, 1996.
We have shown previously that 20 minutes of low volume anoxia ("ischemia") and 20 minutes of "reperfusion" preconditions quiescent pediatric myocyte cultures against damage resulting from 90 minutes of subsequent prolonged "ischemia" and 30 minutes of "reperfusion". The purpose of this study was to assess the roles of adenosine and protein kinase C (PKC) in this preconditioning model. Our results suggest that (1) preconditioned myocytes secrete a protective mediator(s) into the "ischemic" supernatant which is transferrable to other cells and that adenosine is released into the supernatant in quantities sufficient for adenosine receptor activation; (2) preconditioning is inhibited by adenosine receptor antagonism and myocyte protection similar to preconditioning can be achieved with exogenously administered adenosine or adenosine receptor stimulation; (3) brief "ischemic" and adenosine -induced myocyte preconditioning is mimicked by the phorbol ester PMA (PKC agonist) and inhibited by PKC antagonists; and (4) brief "ischemic" and adenosine-induced myocyte preconditioning both induce PKC translocation to myocyte membranes and increase PKC phosphorylation rate. These data suggest that adenosine, released from "ischemic" human pediatric myocytes, mediates preconditioning through activation of protein kinase C. 

Received 31 October 1995; accepted in final form 31 July 1996.
APS Manuscript Number H1022-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996