Dual role of endothelial nitric oxide synthase in oxidized LDL-induced, p66Shc-mediated oxidative stress in cultured human endothelial cells.

ABSTRACT:

Background

The aging gene p66Shc, is an important mediator of oxidative stress-induced vascular dysfunction and disease. In cultured human aortic endothelial cells (HAEC), p66Shc deletion increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability via protein kinase B. However, the putative role of the NO pathway on p66Shc activation remains unclear. This study was designed to elucidate the regulatory role of the eNOS/NO pathway on p66Shc activation.

Methods and results

Incubation of HAEC with oxidized low density lipoprotein (oxLDL) led to phosphorylation of p66Shc at Ser-36, resulting in an enhanced production of superoxide anion (O2-). In the absence of oxLDL, inhibition of eNOS by small interfering RNA or L-NAME, induced p66Shc pho

SUBMITTER: Shi Y 

PROVIDER: S-EPMC4172699 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature