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Dual regulation of caspase activity by hydrogen peroxide: implications for apoptosis
Author(s) -
Hampton Mark B,
Orrenius Sten
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01068-5
Subject(s) - apoptosis , caspase , hydrogen peroxide , jurkat cells , microbiology and biotechnology , chemistry , intrinsic apoptosis , necrosis , caspase 3 , oxidative stress , programmed cell death , biology , biochemistry , immunology , t cell , immune system , genetics
The induction of apoptosis in Jurkat T‐lymphocytes with 50 μM hydrogen peroxide was associated with caspase activation. Caspase activity was first detected 3 h after treatment, and the morphological features of apoptosis were apparent by 6 h. At higher concentrations of hydrogen peroxide there was no detectable caspase activity, and the cells died by necrosis. Cells treated with hydrogen peroxide were impaired in their ability to undergo Fas‐mediated apoptosis. This appeared to be the result of direct inhibition of the cysteine‐dependent caspases. The cells were able to recover and undergo apoptosis at later times. Therefore, hydrogen peroxide has two distinct effects. It initially inhibits 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 discuss the physiological implications of cells having to maintain a reducing environment during apoptosis to allow the caspases to function.