期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 66, 期 7, 页码 1309-1319出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-9001-1
关键词
Histidine decarboxylase; hypoxia; mast cell; hypoxia inducible factor-1; histamine
资金
- Ministry of Science & Technology (MoST)/Korea Science & Engineering Foundation (KOSEF) through the Vestibulocochlear Research Center (VCRC) [R13-2002-055-00000-0]
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-1 alpha, 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-1 alpha prevents hypoxic induction of HDC in BMMCs. In conclusion, these results demonstrate that hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1.
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