Protein kinase C inhibitors produce mitochondrial flavoprotein oxidation in cardiac myocytes. Anesth Analg 2004 Nov;99(5):1316-1322
Date
10/27/2004Pubmed ID
15502023DOI
10.1213/01.ANE.0000135636.45389.E6Scopus ID
2-s2.0-6444236250 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Inhibition of protein kinase C (PKC) antagonizes ischemic preconditioning of myocardium. Opening of mitochondrial adenosine triphosphate (ATP)-dependent potassium (mitoK(ATP)) channels and subsequent oxidation of mitochondria are known to contribute to ischemic preconditioning. We therefore tested the effects of PKC inhibitors on flavoprotein oxidation, measured by flavoprotein fluorescence, as an index of mitoK(ATP) activity in ventricular myocytes from guinea pigs. The PKC inhibitors chelerythrine (1 and 5 microM) and bisindolylmaleimide (100 and 400 nM) strongly increased flavoprotein oxidation in a dose-dependent manner. Specific inhibition of PKC-delta by rottlerin produced persistent flavoprotein oxidation. Inhibition of the production of inositol (1,4,5)-triphosphate by neomycin (0.5 mM) abolished chelerythrine- but not rottlerin-induced flavoprotein oxidation. Inhibition of PKC promotes flavoprotein oxidation via production of inositol (1,4,5)-triphosphate, possibly through the PKC-delta isoform. We speculate that although a certain degree of mitochondrial flavoprotein oxidation causes cardioprotective effects, excessive and/or persistent oxidation abolishes any beneficial actions. Instead of a simple mediator, PKC may act as a regulator of the mitoK(ATP) channel to prevent excessive mitochondrial oxidation.
Author List
Kohro S, Hogan QH, Warltier DC, Bosnjak ZJAuthor
Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetophenonesAlkaloids
Animals
Benzophenanthridines
Benzopyrans
Calibration
Cell Separation
Female
Flavoproteins
Guinea Pigs
In Vitro Techniques
Indoles
Inositol 1,4,5-Trisphosphate
Male
Maleimides
Mitochondria, Heart
Myocytes, Cardiac
Neomycin
Oxidation-Reduction
Phenanthridines
Protein Kinase C
Protein Kinase C-delta
Protein Synthesis Inhibitors
Spectrometry, Fluorescence
