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Redox catalysts as sensitisers towards oxidative stress
Author(s) -
Giles Niroshini M,
Gutowski Nick J,
Giles Gregory I,
Jacob Claus
Publication year - 2003
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(02)03890-5
Subject(s) - oxidative stress , zinc finger , transcription factor , chemistry , glutathione , apoptosis , microbiology and biotechnology , programmed cell death , redox , glutathione peroxidase , cysteine , peroxidase , biochemistry , biology , superoxide dismutase , enzyme , gene , organic chemistry
The predominance of oxidative stress in many tumour cell environments provides a means to selectively target these cells via protein oxidation. The zinc fingers of transcription factors utilise cysteine thiols for structural zinc coordination. Redox control of DNA binding regulates transcription and therefore the overall rates of proliferation, apoptosis and necrosis in the carcinoma. We report here the adverse effects of glutathione peroxidase (GPx) mimics towards zinc finger motifs and PC12 cell survival. Nanomolar catalyst concentrations facilitated H 2 O 2 ‐induced oxidation of an Sp1 transcription factor fragment. In PC12 cells GPx catalysis triggered a significant increase in cell death, correlating with severity of oxidative stress. As a consequence, we conclude that GPx mimics are potential chemotherapeutic agents.