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

被引:44
作者
Jeong, H. J. [2 ]
Moon, P. D.
Kim, S. J. [1 ]
Seo, J. U. [3 ]
Kang, T. H. [3 ]
Kim, J. J. [3 ]
Kang, I. C. [2 ]
Um, J. Y.
Kim, H. M.
Hong, S. H. [1 ]
机构
[1] Wonkwang Univ, Coll Pharm, VestibuloCochlear Res Ctr, Iksan 570749, Jeonbuk, South Korea
[2] Hoseo Univ, Biochip Res Ctr, Asan 336795, Chungnam, South Korea
[3] Kyung Hee Univ, Dept Pharmacol, Inst Oriental Med, Coll Oriental Med,Canc Prevent Mat Dev Res Ctr, Seoul 130701, South Korea
关键词
Histidine decarboxylase; hypoxia; mast cell; hypoxia inducible factor-1; histamine; MAST-CELL LINE; GENE-EXPRESSION; HISTAMINE; INDUCTION; FACTOR-1-ALPHA; HIF-1-ALPHA;
D O I
10.1007/s00018-009-9001-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1309 / 1319
页数:11
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