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Transient receptor potential vanilloid type 1 is vital for (−)‐epigallocatechin‐3‐gallate mediated activation of endothelial nitric oxide synthase
Author(s) -
Guo BeiChia,
Wei Jeng,
Su KuoHui,
Chiang AnNa,
Zhao JinFeng,
Chen HsiangYing,
Shyue SongKun,
Lee TzongShyuan
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400699
Subject(s) - transient receptor potential channel , nitric oxide , nitric oxide synthase , chemistry , endothelial nitric oxide synthase , transient (computer programming) , nitric oxide synthase type iii , receptor , biochemistry , pharmacology , biophysics , medicine , biology , enos , organic chemistry , computer science , operating system
Scope 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. Methods and 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. Conclusion 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.