ミトコンドリア膜結合性グルタチオントランスフェラーゼのシクロスポリン等のMPT阻害剤による抑制

抄録

Effect of mitochondrial permeability transition (MPT) inhibitors on mitochondrial membrane-bound glutathione transferase (mtMGST1) in rat liver was investigated in vitro. When mitochondria were incubated with MPT inhibitors such as cyclosporin A (CsA), bongkrekic acid (BGK), ADP or ATP, mtMGST1 activity was decreased dose dependently and the 50% inhibition concentration (IC50) was 1μM (CsA), 70μM ( BGK), 5mM (ADP), and 4mM (ATP). The inhibitory action of MPT inhibitors on mtMGST1 was not observed in the presence of detergents such as Triton X-100 or NonidetP-40. On the contrary, GST inhibitors cibacron blue and S-hexylglutathione decreased the mtMGST1 activity in the absence or presence of detergents. Although mtMGST1 was detected both in the inner (IMM) and outer mitochondrial membranes (OMM), only mtMGST1 activity in IMM was inhibited by the MPT inhibitors in which the inhibitory action was also disappeared in the presence of detergents. Since CsA binds to cyclophilin D (Cyp-D) in the mitochondrial matrix whereas ADP and BKA bind to adenine nucleotide translocator (ANT ) in the IMM, these results suggest that mtMGST1activity in IMM is modulated through ANT and/or Cyp-D.