title: MRE-binding transcription factor-1 is activated during endotoxemia: a central role for metallothionein.
abstract: Endotoxin (LPS) has been established to induce hepatic metallothionein (MT), but the specific role of MT remains unknown. In this study, we examined whether MT can modulate MTF-1 activity during endotoxemia. Treatment with IL-6, the main mediator of MT induction during endotoxemia, enhanced the expression of the MRE(d)-driven reporter gene. MTF-1 DNA-binding activity was increased 16-24 h after LPS administration in wild-type mice, while no such activation was observed in MT-null mice during the same period. The expression of alpha(1)-acid glycoprotein (AGP) mRNA, an RNA regulated by MTF-1, was lower in MT-null than in wild-type mice. Our results suggested that MTF-1 was activated during endotoxemia. MT can act as an activator of MTF-1, and MT can induce MTF-1 targeted gene expression during endotoxemia.
authors.affiliation: Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kimura
authors.forename: Norio
authors.initials: N
authors.lastname: Itoh
authors.forename: Miyako
authors.initials: M
authors.lastname: Takehara
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Oguro
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ishizaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D019446:Endotoxemia / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009961:Orosomucoid / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D000097809:Transcription Factor MTF-1
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008668:Metallothionein; D009961:Orosomucoid; D012333:RNA, Messenger; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1