title: Transient receptor potential vanilloid type 1 is vital for (-)-epigallocatechin-3-gallate mediated activation of endothelial nitric oxide synthase.
abstract: METHODS
  Epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, has beneficial effects on physiological functions of endothelial cells (ECs), yet the detailed mechanisms are not fully understood. In this study, we investigated the role of transient receptor potential vanilloid type 1 (TRPV1), a ligand-gated nonselective calcium channel, in EGCG-mediated endothelial nitric oxide (NO) synthase (eNOS) activation and angiogenesis.
  
  
  RESULTS
  In ECs, treatment with EGCG time-dependently increased the intracellular level of Ca(2+) . Removal of extracellular calcium (Ca(2+) ) by EGTA or EDTA or inhibition of TRPV1 by capsazepine or SB366791 abrogated EGCG-increased intracellular Ca(2+) level in ECs or TRPV1-transfected HEK293 cells. Additionally, EGCG increased the phsophorylation of eNOS at Ser635 and Ser1179, Akt at Ser473, calmodulin-dependent protein kinase II (CaMKII) at Thr286 and AMP-activated protein kinase (AMPK) at Thr172, all abolished by the TRPV1 antagonist capsazepine. EGCG-induced NO production was diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor), and compound C (an AMPK inhibitor). Moreover, blocking TRPV1 activation prevented EGCG-induced EC proliferation, migration, and tube formation, as well as angiogenesis in Matrigel plugs in mice.
  
  
  CONCLUSIONS
  EGCG may trigger activation of TRPV1-Ca(2+) signaling, which leads to phosphorylation of Akt, AMPK, and CaMKII; eNOS activation; NO production; and, ultimately, angiogenesis in ECs.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Bei-Chia
authors.initials: BC
authors.lastname: Guo
authors.forename: Jeng
authors.initials: J
authors.lastname: Wei
authors.forename: Kuo-Hui
authors.initials: KH
authors.lastname: Su
authors.forename: An-Na
authors.initials: AN
authors.lastname: Chiang
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Zhao
authors.forename: Hsiang-Ying
authors.initials: HY
authors.lastname: Chen
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013662:Tea / Q000737:chemistry
chemical_list: D000813:Anilides; D002934:Cinnamates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D013662:Tea; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium
keywords: Angiogenesis; Ca2+; Endothelial cells; Endothelial nitric oxide synthase; Epigallocatechin-3-gallate; Transient receptor potential vanilloid type 1