Sulfaphenazole attenuates myocardial cell apoptosis accompanied with cardiac ischemia-reperfusion by suppressing the expression of BimEL and Noxa.

Abstract

We previously reported the administration of a potent cytochrome P450 inhibitor, sulfaphenazole (SPZ), to suppress oxidative stress and the extension of myocardial infarct size in a rat model of cardiac ischemia-reperfusion (I/R). The aim of this study was to investigate the effects of SPZ on the myocardial cell apoptosis induced by I/R in rats. I/R injury was evoked by ligation of the left anterior descending coronary artery for 1 h, followed by reperfusion for 3 h. TUNEL-positive nuclei were detected and nucleosomal DNA fragmentation was observed 3 h after reperfusion. The administration of SPZ largely suppressed the cardiac DNA fragmentation induced by I/R. A pan-caspase inhibitor, z-VAD-fmk, had no effect on DNA fragmentation. Caspase-3/7 was not activated 3 h after reperfusion. Decreases in the mitochondrial membrane potential and cytochrome c release from the mitochondria to cytosol were detected 3 h after reperfusion. The expression levels of BimEL and Noxa were elevated 3 h after reperfusion. These phenomena were suppressed by the administration of SPZ. Taken together, treatment with SPZ could attenuate the myocardial cell apoptosis accompanied with I/R by inhibiting the mitochondrial dysfunction due to decreases in the expression of BimEL and Noxa.

• Authors: Yasuhiro Ishihara, Norio Shimamoto
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 119 Issue 3 Pg. 251-9 ( 2012) ISSN: 1347-8648 [Electronic] Japan
• PMID: 22785021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Bcl-2-Like Protein 11
• Bcl2l11 protein, rat
• Membrane Proteins
• Pmaip1 protein, rat
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• Sulfaphenazole
• Cytochromes c
• Caspase 3
• Caspase 7

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Bcl-2-Like Protein 11
• Caspase 3 (metabolism)
• Caspase 7 (metabolism)
• Cytochromes c (metabolism)
• Cytosol (drug effects, metabolism)
• DNA Fragmentation (drug effects)
• In Situ Nick-End Labeling (methods)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Membrane Proteins (metabolism)
• Mitochondria (drug effects, metabolism)
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy, metabolism, pathology)
• Sulfaphenazole (pharmacology)