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Tannin 1‐α‐ O ‐galloylpunicalagin induces the calcium‐dependent activation of endothelial nitric‐oxide synthase via the phosphatidylinositol 3‐kinase/Akt pathway in endothelial cells
Author(s) -
Chen LihGeeng,
Liu YenChin,
Hsieh ChiaWen,
Liao BeingChyuan,
Wung BeingSun
Publication year - 2008
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.200700335
Subject(s) - phosphatidylinositol , endothelial nitric oxide synthase , protein kinase b , chemistry , nitric oxide , nitric oxide synthase , nitric oxide synthase type iii , microbiology and biotechnology , pi3k/akt/mtor pathway , kinase , signal transduction , biochemistry , enzyme , biology , enos , organic chemistry
Many polyphenols have been found to increase endothelial nitric oxide (NO) production. In our present study, we investigated the effects of 1‐α‐ O ‐galloylpunicalagin upon endothelial nitric oxide synthase (eNOS) activity in endothelial cells (ECs). Both 1‐α‐ O ‐galloylpunicalagin and punicalagin induced NO production in a dose‐dependent manner in ECs. Despite having similar chemical structures, punicalagin induced lower levels of NO production than 1‐α‐ O ‐galloylpunicalagin. After 1‐α‐ O ‐galloylpunicalagin addition, a rise in the intracellular Ca 2+ concentration preceded NO production. The Ca 2+ ionophore A23187 stimulated eNOS phosphorylation and augmented NO production. Pretreatment with Ca 2+ chelators inhibited 1‐α‐ O ‐galloylpunicalagin‐induced eNOS phosphorylation and NO production. Treatment with 1‐α‐ O ‐galloylpunicalagin did not alter the eNOS protein levels but, unlike punicalagin, induced a sustained activation of eNOS Ser 1179 phosphorylation. 1‐α‐ O ‐galloylpunicalagin was also found to activate ERK1/2, JNK and Akt in ECs. Moreover, simultaneous treatment of these cells with specific phosphatidylinositol‐3‐kinase inhibitors significantly inhibited the observed increases in eNOS activity and phosphorylation levels. In contrast, the inhibition of (ERK)1/2, JNK and p38 had no influence on eNOS Ser 1179 phosphorylation. Our present results thus indicate that the 1‐α‐ O ‐galloylpunicalagin‐induced calcium‐dependent activation of eNOS is primarily mediated via a phosphatidylinositol 3‐kinase/Akt‐dependent increase in eNOS activity, and occurs independently of the eNOS protein content.