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- Title
Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression.
- Authors
Jeong, H. J.; Moon, P. D.; Kim, S. J.; Seo, J. U.; Kang, T. H.; Kim, J. J.; Kang, I. C.; Um, J. Y.; Kim, H. M.; Hong, S. H.
- 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-1α, 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-1α prevents hypoxic induction of HDC in BMMCs. In conclusion, these results demonstrate that hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1.
- Subjects
HISTIDINE; HISTAMINE; INFLAMMATION; GROWTH factors; MAST cells; CELL lines; HYPOXEMIA
- Publication
Cellular & Molecular Life Sciences, 2009, Vol 66, Issue 7, p1309
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-009-9001-1