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Induction of cellular necrosis by the glutathione peroxidase mimetic ebselen
Author(s) -
Guérin Paul J.,
Gauthier Eric R.
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10500
Subject(s) - ebselen , cycloheximide , apoptosis , programmed cell death , pharmacology , antioxidant , chemistry , necrosis , neuroprotection , glutathione , glutathione peroxidase , biochemistry , biology , medicine , enzyme , superoxide dismutase , protein biosynthesis
The selenium‐based compound ebselen is a powerful antioxidant, a potent anti‐inflammatory agent and a potential neuroprotective compound. Several studies have demonstrated that part of the biological effect of ebselen is the result of the inhibition of apoptosis. We show in this report that ebselen induced the necrotic cell death of Sp2/0‐Ag14 hybridoma cells. This process was rapid, with over 90% of the cells being dead after a 2 h exposure to 50 μM ebselen. The toxic effect of ebselen could not be prevented by the caspase inhibitor Z‐VAD‐fmk but could be blocked with thiol‐containing compounds. Interestingly, ebselen addition completely prevented caspase activation in cycloheximide‐treated Sp2/O‐Ag14 cells, indicating that this antioxidant interferes with the apoptotic machinery. Our results indicate that some cell types are acutely sensitive to the toxic effect of ebselen, and that ebselen‐induced cell death interferes with apoptotic processes. These observations are of particular importance since ebselen is currently used in clinical trials for possible use as therapeutic agent for stroke. J. Cell. Biochem. 89: 203–211, 2003. © 2003 Wiley‐Liss, Inc.