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Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression

Author:
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.
Source:
Cellular and molecular life sciences 2009 v.66 no.7 pp. 1309-1319
ISSN:
1420-682X
Subject:
cell growth, histamine, histidine, histidine decarboxylase, humans, hypoxia, hypoxia-inducible factor 1, inflammation, mast cells, mice, transcription (genetics)
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.
Agid:
2163010