Faculty Collaboration Database

PKC-delta inhibition does not block preconditioning-induced preservation in mitochondrial ATP synthesis and infarct size reduction in rats. Basic Res Cardiol 2002 Jan;97(1):47-54

Date

05/10/2002

Pubmed ID

11998977

DOI

10.1007/s395-002-8387-x

Scopus ID

2-s2.0-0036150173 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

We have previously demonstrated that cardioprotection induced by the infusion of a selective delta1-opioid agonist is mediated by the specific translocation of PKC-delta to the mitochondria in in vivo rat hearts and via opening of the mitochondrial KATP channel. Ischemic preconditioning (IPC) is also thought to involve the translocation of specific isoforms of PKC and KATP channel activation. Therefore, we utilized the PKC-delta selective antagonist, rottlerin, to assess the effect of inhibition of this isozyme on cardioprotection induced by one-cycle of IPC prior to 30 minutes of ischemia and 2 hours of reperfusion. Infarct size (IS) was determined by tetrazolium chloride staining and expressed as a percent of the area at risk (AAR). Non-preconditioned control animals had an IS/AAR of 59.7 +/- 1.6. IPC significantly reduced the extent of myocardial infarction (6.3 +/- 1.4). Rottlerin, 0.3 mg/kg, did not alter IS/AAR in control animals (55.0 +/- 5.6), and had no significant effect on IS/AAR in preconditioned animals (14.4 +/- 3.8). Additionally, we demonstrated, using a luciferase-based assay to determine the rate of ATP synthesis and state of mitochondrial bioenergetics, that IPC preserves ATP synthesis in the ischemic myocardium and that this preservation is attenuated by the isoform non-selective PKC inhibitor, chelerythrine, but not by the delta-selective antagonist, rottlerin. These data suggest that PKC-delta does not play an important role in IPC and that differences in isoform importance are evident during pharmacological versus ischemia-induced preconditioning.

Author List

Fryer RM, Hsu AK, Wang Y, Henry M, Eells J, Gross GJ

Author

Janis Eells PhD Professor in the Biomedical Sciences department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Acetophenones
Adenosine Triphosphate
Alkaloids
Animals
Benzophenanthridines
Benzopyrans
Enzyme Inhibitors
Hemodynamics
Immunohistochemistry
Ischemic Preconditioning, Myocardial
Isoenzymes
Male
Mitochondria, Heart
Myocardial Infarction
Phenanthridines
Protein Kinase C
Protein Kinase C-delta
Rats
Rats, Wistar