Involvement of peripheral benzodiazepine receptor in the regulation of rat cardiac mitochondria permeability transition

Aim To investigate the role of peripheral benzodiazepine receptor in rat cardiac mitochondrial permeability transition.Methods The isolated rat cardiac mitochondria were incubated with different doses(50,100,200 μmol·L-1) of PBR antagonist 1-(2-chlorophenyl-N-methyl-1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195). In additional group(CsA group), 5 μmol·L-1 cyclosporine A (CsA), an inhibitor of MPT was added 5 minutes before the addition of 100 μmol·L-1 PK 11195. Negative control group(Con group) was given none treatment. Positive control group(Ca2+ group) was given 150 μmol·L-1 CaCl2. The absorbanceat 520 nm(Abs 520 nm) was monitored with a split-beam spectrophotometer at 30℃ for 10 min. The mitochondrial ultrastructure was assessed by transmission electron microscopy. Mitochondrial cytochrome C release was demonstrated by Western Blotting.Results PK11195 triggered large-amplitude mitochondrial swelling in a dose dependent manner(vs Con group,P0.05, P0.01), There were significant differences among different dose of PK 11195(P0.05); PK11195 caused mitochondria ultrastructural abnormalities, the release of CytoC from mitochondria into the cytosol(vs Con group,P0.01); In CsA group, most of mitochondria displayed the characteristic ultrastructure of the intact organelle, there was less release of mitochondria cytochrome C from mitochondria(vs 100 μmol·L-1 group,P0.05).Conclusion PBR is involved in the regulation of MPT, which can regulate cardiac mitochondria injury, appears of a novel target for cardioprotection.