Irreversible inactivation of calcium-dependent proteinases from rat liver by biological disulfides

The effect of low-molecular-mass biological disulfides and their related reduced compounds on the activity of two calcium-dependent neutral proteinases (calpains) from rat liver has been investigated. L-Cystine and L-cystamine bring about the inactivation of both enzymes, while the related reduced compounds L-cysteine and L-cysteamine are without effect. Calpain II is more sensitive to the inactivating effect of glutathione disulfide in comparison with calpain I. The inactivation rates of both calpains depend on the concentration of glutathione disulfide. Reduced glutathione, added at physiological concentration (5 mM), neither affects the proteinase activities nor protects the enzymes from the inactivating effect of glutathione disulfide. The enzymes inactivated by biological disulfides cannot be restored by a large excess of a reducing thiolic compound (dithiothreitol). It is suggested that calcium-dependent proteinases might be inactivated also in vivo by enhanced level of glutathione disulfide.