title: Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression.
abstract: Histidine decarboxylase (HDC) catalyzes the formation of histamine from histidine. Histamine has various effects in physiological and pathological reactions, such as inflammation, cell growth, and neuro-transmission. We investigated the role of hypoxia-inducible factor (HIF)-1 on hypoxia-induced HDC expression in human mast cell line, HMC-1 cells and mouse bone marrow-derived mast cells (BMMCs). Hypoxia significantly increased histamine production. HDC expression and activity were induced by hypoxia. Additionally, when cells were transfected with a native form of HIF-1alpha, hypoxia could induce higher HDC expression than in the nontransfected cell. HIF-1 binding activity for HDC 5' flanking region (HFR) was similar to that for the hypoxia-responsive element. Using HDC promoter deletion analysis, we also demonstrated that HFR was regulated by HIF-1 activation. In addition, depletion of HIF-1alpha prevents hypoxic induction of HDC in BMMCs. In conclusion, these results demonstrate that hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1.
authors.affiliation: Biochip Research Center, Hoseo University, 165 Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Jeong
authors.forename: P D
authors.initials: PD
authors.lastname: Moon
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: J U
authors.initials: JU
authors.lastname: Seo
authors.forename: T H
authors.initials: TH
authors.lastname: Kang
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: I C
authors.initials: IC
authors.lastname: Kang
authors.forename: J Y
authors.initials: JY
authors.lastname: Um
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Hong
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006632:Histamine / Q000096:biosynthesis*; D006640:Histidine Decarboxylase / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D006632:Histamine; D006640:Histidine Decarboxylase