DUAL REGULATION OF CASPASE ACTIVITY BY HYDROGEN-PEROXIDE - IMPLICATIONS FOR APOPTOSIS

The induction of apoptosis in Jurkat T-lymphocytes with 50 mu M hydrog en peroxide was associated with caspase activation, Caspase activity w as first detected 3 h after treatment, and the morphological features of apoptosis were apparent by 6 h, At higher concentrations of hydroge n peroxide there,vas no detectable caspase activity, and the cells die d by necrosis. Cells treated with hydrogen peroxide were impaired in t heir ability to undergo Fas-mediated apoptosis, This appeared to be th e result of direct inhibition of the cysteine-dependent caspases, The cells mere able to recover and undergo apoptosis at later times, There fore, hydrogen peroxide has two distinct effects, It initially inhibit s the caspases and delays apoptosis, Then, depending on the degree of the initial oxidative stress, the caspases are activated and the cells die by apoptosis, or they remain inactive and necrosis occurs, We dis cuss the physiological implications of cells having to maintain a redu cing environment during apoptosis to allow the caspases to function. ( C) 1997 Federation of European Biochemical Societies.