Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression.
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.
Jeong
H J
HJ
Biochip Research Center, Hoseo University, 165 Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea.
Moon
P D
PD
Kim
S J
SJ
Seo
J U
JU
Kang
T H
TH
Kim
J J
JJ
Kang
I C
IC
Um
J Y
JY
Kim
H M
HM
Hong
S H
SH
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
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D006632:Histamine; D006640:Histidine Decarboxylase