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Effect of cobalt treatment on cell growth and mitochondrial DNA damage in HEK293 acutely exposed to hydrogen peroxide
Author(s) -
Nomura Yasutomo,
Fujiwara Hiroyuki,
Ito Kohei,
Sato Michihiko,
Takahashi Eiji,
Hozumi Yasukazu,
Feng Zhonggang,
Nakamura Takao
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.20.5.a1457-b
Subject(s) - reactive oxygen species , apoptosis , hydrogen peroxide , mitochondrial dna , dna damage , cytochrome c , mitochondrion , chemistry , hypoxia (environmental) , microbiology and biotechnology , cell , cell growth , oxygen , biology , biochemistry , dna , gene , organic chemistry
Severity of ischemia/reperfusion injury accompanied with generation of reactive oxygen species is reduced by hypoxic preconditioning, the precise mechanisms of which are not completely understood. Recently, several authors suggested the pathway via hypoxia‐inducible factor‐1α (HIF‐1α). The activation reduced the number of ischemia‐induced apoptotic cells through the suppression of apoptosis signaling of cytochrome c release. Reactive oxygen species cause not only apoptosis via cytochrome c , but also mitochondrial DNA (mtDNA) damage. In this study, we determined cell growth and mtDNA damage in HEK293 cells exposed to H 2 O 2 as pretreated with cobalt to mimic hypoxic preconditioning. When cells were treated with 0.2~0.4 mM H 2 O 2 , cell growth was suppressed, and mtDNA was damaged dependent on H 2 O 2 concentration. When 0.4 mM H 2 O 2 was exposed to cells where HIF‐1α was induced with 100 μM CoCl 2 , mtDNA damage was suppressed, and cell number 4 days after H 2 O 2 exposure (15.7 % against no exposure) was significantly greater than that without cobalt treatment (3.7 %). These results suggest that cobalt‐induced HIF‐1α activity ameliorates suppression of cell growth through protecting mtDNA damage caused by H 2 O 2 .