Genome wide analysis of TNF-inducible genes reveals that antioxidant enzymes are induced by TNF and responsible for elimination of ROS.
We recently showed that TNF induces accumulation of reactive oxygen species (ROS) that mediates necrosis in murine embryonic fibroblasts (MEFs) derived from TRAF2- and TRAF5-double deficient (DKO) mice. To elucidate the defects that subsequently cause accumulation of ROS in DKO MEFs, we compared gene expression profiles of wild-type and DKO MEFs before and after TNF stimulation using cDNA microarrays. Interestingly, many antioxidant enzymes are induced by TNF in wild-type MEFs, induction of these genes is impaired in DKO MEFs. Taken that TNF induces accumulation of ROS in DKO, but not wild-type MEFs, upregulation of antioxidant enzyme(s) might play a crucial role in elimination of ROS.
Sasazuki
Tomonari
T
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Okazaki
Tatsuma
T
Tada
Kurisu
K
Sakon-Komazawa
Sachiko
S
Katano
Mitsuo
M
Tanaka
Masao
M
Yagita
Hideo
H
Okumura
Ko
K
Tominaga
Naoko
N
Hayashizaki
Yoshihide
Y
Okazaki
Yasushi
Y
Nakano
Hiroyasu
H
D000818:Animals; D000975:Antioxidants; D004798:Enzymes / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D023281:Genomics; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000975:Antioxidants; D004798:Enzymes; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha