title: Genome wide analysis of TNF-inducible genes reveals that antioxidant enzymes are induced by TNF and responsible for elimination of ROS.
abstract: 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.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Tatsuma
authors.initials: T
authors.lastname: Okazaki
authors.forename: Kurisu
authors.initials: K
authors.lastname: Tada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Sakon-Komazawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Naoko
authors.initials: N
authors.lastname: Tominaga
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
mesh_terms: 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*
chemical_list: D000975:Antioxidants; D004798:Enzymes; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha