Protein kinase c mediates ca2+ induced cardioadaptation to
ischemia-reperfusion injury.
Meldrum, Daniel R., Joseph C. Cleveland, Jr., Max B. Mitchell, Brett
C. Sheridan, Fabia Gamboni-Robertson, Alden H. Harken, Anirban
Banerjee.
Department of Surgery, University of Colorado Health Sciences
Center, Denver, Colorado
APStracts 3:0125R, 1996.
Although protein kinase C (PKC) mediated cardioadaptation to I/R is
accompanied by increased [Ca2+]i, it is unknown whether a pre
-ischemia sarcoplasmic reticulum (SR) Ca2+ release affects PKC
mediated post-ischemia reperfusion (I/R) functional protection. To
study this, crystalloid perfused (Langendorf) Sprague-Dawley rat
hearts were used to assess the effects of a ryanodine (Ry) induced
pre-ischemia Ca2+ load (Ry, 5 nM/2 min, retrograde coronary), 10 min
prior to global I/R (20 min). Ry was administered with and without
each of two different PKC inhibitors (20 uM chelerythrine and 150 nM
bisindolylmaleimide I-HCl). Ry improved myocardial functional
recovery (developed pressure, end diastolic pressure, coronary flow,
and creatine kinase activity), which was eliminated following PKC
inhibition. Immunohistochemical staining for PKC isoforms
demonstrated that Ry induces specific PKC translocation of isoforms
a, d, and z. We conclude that: 1) a pre-ischemia Ca2+ load from the
SR results in post-I/R myocardial functional protection, 2) Ca2+
induced functional protection is PKC regulated via the translocation
of specific isoforms, 3) Ca2+ induced cardioadaptation to I/R injury
may have important therapeutic implications prior to planned ischemic
events such as cardiac allograft preservation and cardiac bypass
surgery.
Received 18 September 1995; accepted in final form 20 March 1996.
APS Manuscript Number R578-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96