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Regulation of ionizing radiation‐induced apoptosis by antioxidant enzyme mimetics
Author(s) -
Park JeenWoo
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a73-d
Subject(s) - ebselen , apoptosis , ionizing radiation , reactive oxygen species , chemistry , microbiology and biotechnology , programmed cell death , antioxidant , glutathione , biochemistry , oxidative stress , peroxidase , glutathione peroxidase , biophysics , superoxide dismutase , enzyme , biology , irradiation , physics , nuclear physics
Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on apoptosis. We investigated the effects of the manganese (III) tetrakis(N‐methyl‐2‐pyridyl)porphyrin (MnTMPyP), a cell permeable SOD mimetic, and ebselen, a glutathione peroxidase mimetic, on ionizing radiation‐induced apoptosis. Upon exposure to 2 Gy of γ‐irradiation, there was a distinct difference between the control cells and the cells pre‐treated with 5 μM MnTMPyP or ebselen for 2 h in regard to apoptotic parameters, cellular redox status, mitochondria function, and oxidative damage to cells. MnTMPyP and ebselen pre‐treated cells showed significant inhibition of apoptotic features such as activation of caspase‐3, up‐regulation of Bax and p53, and down‐regulation of Bcl‐2 compared to control cells upon exposure to ionizing radiation. This study indicates that atioxidant enzyme mimetics may play an important role in regulating the apoptosis induced by ionizing radiation presumably through scavenging of reactive oxygen species.