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Peroxynitrite damages U937 cell DNA via the intermediate formation of mitochondrial oxidants
Author(s) -
Cantoni Orazio,
Guidarelli Andrea
Publication year - 2008
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.116
Subject(s) - peroxynitrite , dephosphorylation , chemistry , reactive oxygen species , u937 cell , peroxynitrous acid , microbiology and biotechnology , dna damage , mitochondrion , superoxide , biochemistry , phosphatase , dna , biology , phosphorylation , apoptosis , enzyme
Eight years ago, we published in this journal the first evidence that peroxynitrite does not directly produce DNA single‐strand breakage in intact U937 cells (Guidarelli et al., IUBMB Life , 50, 195–201). This event was rather attributed to the secondary reactive species produced at the mitochondrial level via a Ca 2+ ‐dependent reaction, in which ubisemiquinone serves as an electron donor. Under these conditions, electrons are directly transferred to molecular oxygen and superoxide/H 2 O 2 , and the ensuing DNA damage can therefore be produced in a time‐ dependent manner for at least 30 min. Formation of H 2 O 2 and DNA single‐strand breaks was therefore dependent on interference with electron transport at the complex III level as well as on mitochondrial Ca 2+ accumulation. Further studies led to the demonstrations that peroxynitrite mobilizes Ca 2+ from the ryanodine receptor. Finally, in U937 cells, a pro‐monocytic cell line sharing with monocytes/macrophages the same signaling events to survive to peroxynitrite, mitochondrial H 2 O 2 promotes inhibition of survival via tyrosine phosphatase activation, leading to ERK1/2 dephosphorylation and thus to upstream inhibition of the survival signaling. © 2008 IUBMB IUBMB Life, 60(11): 753–756, 2008