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Nitrooleate Mediates Nitric Oxide Synthase Activation in Endothelial Cells
Author(s) -
Shin Eunju,
Yeo Eunju,
Lim Jihye,
Chang Yun Hee,
Park Haeryun,
Shim Eugene,
Chung Haeyon,
Hwang Hye Jin,
Chun Jiyeon,
Hwang Jinah
Publication year - 2014
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-014-3893-8
Subject(s) - enos , dephosphorylation , phosphorylation , nitric oxide , hsp90 , chemistry , protein kinase b , caveolin 1 , microbiology and biotechnology , nitric oxide synthase type iii , nitric oxide synthase , biochemistry , heat shock protein , biology , organic chemistry , phosphatase , gene
Nitrated lipids such as nitrooleate (OLA‐NO 2 ) can act as endogenous peroxisome proliferator‐activated receptor gamma (PPARγ) ligands to exert vascular protective effects. However, the molecular mechanisms regarding nitric oxide (NO) production and its regulation are not fully defined in the vasculature. Here, we show that OLA‐NO 2 increased endothelial NO release by modulating activation of endothelial nitric oxide synthase (eNOS) in endothelial cells. Treatment with OLA‐NO 2 (3 μM) increased NO release in a time‐dependent manner. OLA‐NO 2 decreased protein expression of eNOS and caveolin‐1 (Cav‐1) but increased heat shock protein 90 (Hsp90) expression. Immunoprecipitation analysis confirmed that OLA‐NO 2 replaced eNOS/Cav‐1 with eNOS/Hsp90 interaction, resulting in increasing eNOS activity. OLA‐NO 2 also induced eNOS phosphorylation at Ser633 and Ser1177 and eNOS dephosphorylation at Ser113 and Thr495. In addition, OLA‐NO 2 induced phosphorylation of Akt and extracellular signal‐regulated protein kinase (ERK1/2), which might contribute to eNOS activation. Collectively, these results substantiate a new functional role for nitrated fatty acid, demonstrating that OLA‐NO 2 exerts vascular protective effects by increasing NO bioavailability through eNOS phosphorylation/dephosphorylation and interaction with associated proteins such as Hsp90 and Cav‐1.