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ANTI‐APOPTOTIC EFFECT OF ATORVASTATIN, A 3‐HYDROXY‐3‐METHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR, ON CARDIAC MYOCYTES THROUGH PROTEIN KINASE C ACTIVATION
Author(s) -
Tanaka Koichi,
Honda Masaaki,
Takabatake Toshikazu
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.04010.x
Subject(s) - atorvastatin , reductase , chemistry , protein kinase a , pharmacology , apoptosis , myocyte , coenzyme a , kinase , medicine , endocrinology , enzyme , biochemistry
Summary 1. Pleiotropic effects of statins, which are independent of lipid lowering, have been reported. In the present study, we examined the effect of a statin on apoptosis of adult rat cultured cardiac myocytes. We used the protein kinase C (PKC) inhibitors staurosporine (1 µmol/L), chelerythrine (10 µmol/L) and rottlerin (5 µmol/L) to induce myocyte apoptosis. The effect of atorvastatin (10 −7 g/mL), a statin, on myocyte apoptosis induced by these PKC inhibitors was examined. 2. All these PKC inhibitors markedly increased the percentage of terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labeling (TUNEL)‐positive myocytes. This increase was significantly suppressed by atorvastatin treatment. Both chelerythrine and rottlerin induced subcellular translocation of PKCδ and elevated caspase‐3 activity in myocytes. The changes in the subcellular distribution of PKCδ and caspase‐3 activity induced by these PKC inhibitors were suppressed by atorvastatin treatment. 3. The results of the present study suggest that the inhibitory effect of atorvastatin on apoptosis of adult rat cardiac myocytes induced by the PKC inhibitors is through activation of PKCδ pathway.