Hypoxia-Inducible Factor-1α Is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic Stress

被引:64
作者
Liu, XinHua [1 ,2 ]
Pan, LiLong [1 ,2 ]
Zhuo, Yang [1 ,2 ]
Gong, QiHai [1 ,2 ]
Rose, Peter [3 ]
Zhu, YiZhun [1 ,2 ]
机构
[1] Fudan Univ, Dept Pharmacol, Sch Pharm, Shanghai 201203, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai 201203, Peoples R China
[3] Kings Coll London, Pharmaceut Sci Res Div, London SE1 9NH, England
基金
中国国家自然科学基金;
关键词
hydrogen sulfide; angiogenesis; co-culture; hypoxia-inducible factor-1 alpha; vascular endothelial growth factor; GROWTH-FACTOR EXPRESSION; GENE-TRANSCRIPTION; TUMOR ANGIOGENESIS; FACTOR; 1-ALPHA; H2S; PHOSPHORYLATION; HIF-1-ALPHA; PATHWAY; CANCER; RAT;
D O I
10.1248/bpb.33.1550
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Hydrogen sulfide (H2S) is known to have pro-angiogenic properties in mammals. In this study, we examined H2S played the role in pro-angiogenesis mediated by hypoxia-inducible factor (HIF)-1 alpha under hypoxic conditions. Rat brain capillary endothelial cells (ECs) were treated with NaHS (a H2S donor) pretreated vascular smooth muscle cells (VSMCs) conditioned media. ECs proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ECs migration was assessed by chemotaxis chamber assay. Angiogenesis-associated gene expression levels were determined by reverse transcription-polymerase chain reaction (RT-PCR). HIF-1 alpha and vascular endothelial growth factor (VEGF) accumulation was analyzed by Western blotting. HIF-1 binding activity was measured by electrophoretic mobility shift assay (EMSA). We found H2S induced both endothelial proliferation and migration in mimic hypoxic condition. In addition, H2S promoted VEGF and HIF-1 alpha mRNA levels. H2S also significantly upregulated HIF-1 alpha and VEGF protein levels and increased HIF-1 alpha binding activity under hypoxic condition. Our findings suggest that HIF-1/VEGF is involved in H2S promotes proliferation and migration of ECs.
引用
收藏
页码:1550 / 1554
页数:5
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