Mitochondrial sulfhydryl groups under oligomycin-inhibited, aging, and uncoupling conditions: beneficial influence of cardioprotective drugs.

Uncoupling, oligomycin-inhibited, and aging/swelling conditions comprise three models for mitochondrial dysfunction. In these models, the effects of cardioprotective agents on rat heart mitochondrial membrane -SH reactivity have been studied. For -SH detection two different chromophores were used: dithionitrobenzoate (NbS2) and monobromobimane (MB). The objective of this study is to reveal the influence of three cardioprotective substances against the loss of membrane -SH reactivity: (i) The thiol reagent 2-mercaptopropionylglycine (MPG) prevents the decrease of thiols caused by carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), aging, and oligomycin measured with MB and NbS2, and the diminution by oleate detected with MB. The small amount of MPG (6 nmol/mg protein), necessary for the protection, agrees with oligomycin sensitivity of the -SH groups concerned. (ii) The active metabolite of molsidomine, 3-morpholinosydnonimine (SIN-1), protects against the decrease of thiols by FCCP, oleate, and aging monitored with MB. In the case of oligomycin -SH groups accessible to NbS2 are protected. (iii) Another antianginal drug, isosorbidedinitrate (ISDN) does not protect membrane thiol groups. In contrast to SIN-1, ISDN probably requires enzymatic activation. It is suggested that MPG as well as SIN-1 may help to restitute the original -SH status of the mitochondrial membrane.