title: The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation.
abstract: OBJECTIVE
  Hydrogen sulfide (H(2)S) has been reported to be a gasotransmitter which regulates cardiovascular homeostasis. The present study aims to examine the hypothesis that hydrogen sulfide is able to promote angiogenesis.
  
  
  METHODS
  Angiogenesis was assessed using in vitro parameters (i.e. endothelial cell proliferation, adhesion, transwell migration assay, scratched wound healing and formation of tube-like structure) and in vivo by assessing neovascularization in mice. Phosphorylation of Akt was measured using Western blot analysis.
  
  
  RESULTS
  Exogenously administered NaHS (H(2)S donor) concentration-dependently (10-20 micromol/l) increased cell growth, migration, scratched wound healing and tube-like structure formation in cultured endothelial cells. These effects of NaHS on endothelial wound healing and tube-like structure formation were prevented by either the phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002 (5 micromol/l) or transfection of a dominant-negative mutant of Akt. NaHS increased Akt phosphorylation and this effect was also blocked by either LY 294002 or wortmannin (25 nmol/l). NaHS did not significantly alter the levels of vascular endothelial growth factor, mRNA expression of fibroblast growth factor and angiopoietin-1, or nitric oxide metabolites. NaHS treatment (10 and 50 micromol kg(-1) day(-1)) significantly promoted neovascularization in vivo in mice.
  
  
  CONCLUSIONS
  The present study reports a novel proangiogenic role of H(2)S which is dependent on activation of Akt.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Cai
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Wang
authors.forename: Philip Keith
authors.initials: PK
authors.lastname: Moore
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Jin
authors.forename: Tai
authors.initials: T
authors.lastname: Yao
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Zhu
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins; D039421:Integrin alpha2 / Q000032:analysis / Q000378:metabolism; D019012:Integrin beta1 / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012097:Repressor Proteins; D013194:Staining and Labeling; D013268:Stimulation, Chemical; D000077022:Survivin; D046509:Tissue Culture Techniques; D000077191:Wortmannin; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000730:Androstadienes; C117749:Birc5 protein, mouse; D002867:Chromones; D051034:Inhibitor of Apoptosis Proteins; D039421:Integrin alpha2; D019012:Integrin beta1; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012097:Repressor Proteins; D000077022:Survivin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; D006862:Hydrogen Sulfide