Peripheral benzodiazepine receptor agonist Ro5-4864 inhibits mitochondrial permeability transition in rat heart / 生理学报
Acta Physiologica Sinica
; (6): 13-18, 2007.
Article
em Zh
| WPRIM
| ID: wpr-258694
Biblioteca responsável:
WPRO
ABSTRACT
Opening of mitochondrial permeability transition (MPT) pores leads to mitochondrial injury during oxidative stress. The peripheral benzodiazepine receptor (PBR) located at mitochondrial outer-membrane has been shown to be involved in several mitochondrial functions. In the present study, we used Ro5-4864, a PBR agonist, to test if activation of PBR could prevent MPT pore opening during Ca(2+) overloading. Cardiac mitochondria isolated from Sprague-Dawley rats were treated by 150 mmol/L Ca(2+) to induce MPT. Ro5-4864 (50, 100 and 200 micromol/L) was added into incubation buffer before adding 150 micromol/L Ca(2+). In additional group, atractyloside (ATR, 20 micromol/L), an opener of MPT pores was added 5 min before the addition of 100 micromol/L Ro5-4864. The change of absorbance at 520 nm was monitored with a spectrophotometer at 30 degrees C for 10 min. Western blot was used to detect cytochrome C loss. The mitochondrial membrane potential was monitored with the fluorescence dye JC-1. Ro5-4864 inhibited the decrease of absorbance at 520 nm compared to that in the untreated Ca(2+) group (P<0.01, P<0.05). In the presence of ATR, Ro5-4864 was not able to prevent MPT anymore. Opening of MPT pores by Ca(2+) decreased the content of cytochrome C in mitochondria, but increased cytochrome C content in cytosol. Ro5-4864 preserved cytochrome C content in mitochondria and led to less cytochrome C release to cytosol. ATR treatment reversed the protective effect of Ro5-4864 on cytochrome C content. Opening of MPT pores led to mitochondrial depolarization, whereas Ro5-4864 treatment maintained mitochondrial membrane potential. Thus, prevention of MPT by activation of PBR during calcium overloading maintains mitochondrial cytochrome C content and membrane potential. Activation of PBR during cardiac ischemia and reperfusion may be an alternative way for cardioprotection.
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Índice:
WPRIM
Assunto principal:
Farmacologia
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Fisiologia
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Efeitos da Radiação
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Atractilosídeo
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Benzodiazepinonas
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Proteínas de Transporte
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Ratos Sprague-Dawley
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Receptores de GABA-A
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Proteínas de Transporte da Membrana Mitocondrial
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Potencial da Membrana Mitocondrial
Limite:
Animals
Idioma:
Zh
Revista:
Acta Physiologica Sinica
Ano de publicação:
2007
Tipo de documento:
Article