Hypoxia-inducible factor-1α is involved in the pro-angiogenic effect of hydrogen sulfide under hypoxic stress.
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)-1alpha 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-1alpha 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-1alpha mRNA levels. H2S also significantly upregulated HIF-1alpha and VEGF protein levels and increased HIF-1alpha binding activity under hypoxic condition. Our findings suggest that HIF-1/VEGF is involved in H2S promotes proliferation and migration of ECs.
Liu
XinHua
X
Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Pan
LiLong
L
Zhuo
Yang
Y
Gong
QiHai
Q
Rose
Peter
P
Zhu
YiZhun
Y
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000633:toxicity*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000502:physiology
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D006862:Hydrogen Sulfide