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.
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Received 02 January 2009; accepted 09 February 2009
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Jeong, H.J., Moon, P.D., Kim, S.J. et al. Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression. Cell. Mol. Life Sci. 66, 1309–1319 (2009). https://doi.org/10.1007/s00018-009-9001-1
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DOI: https://doi.org/10.1007/s00018-009-9001-1