Hydrogen Peroxide Activates Endothelial Nitric-oxide Synthase through Coordinated Phosphorylation and Dephosphorylation via a Phosphoinositide 3-Kinase-dependent Signaling Pathway

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…(Massaro et al 1989). In the absence of (Drummond et al 2000;Thomas et al 2002;Cai et al 2003b;Kuzkaya et al 2003;Landmesser et al 2003 This was reduced to 24.9 ± 8.1% in the presence of N G -nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS activity (n=6, p<0.001, (Pritchard et al 1995;Munzel et al 2000;Pritchard et al 2001)). These findings suggest that treatment with H 2 O 2 resulted in increased NOS activity in PAEC.…”

“…An increase in peroxynitrite (ONOO -) formation due to increased availability of NO with eNOS upregulation and H 2 O 2 stimulation of eNOS activity and increased NO production may also contribute (Thomas et al 2002;Cai et al 2003b Quijano et al 2001;Radi et al 2001). In part due to the scavenging of O 2 .-by SOD, which is thought to be dominant until O 2 .-and NO levels are similar, at that time ONOOformation becomes the dominant reaction Quijano et al 2001; Wolin et al 2002;Cai et al 2003b;Kuzkaya et al 2003).…”

“…When eNOS-transfected PAEC were exposed to H 2 O 2 , 57.7 ± 6.0% of nuclei exhibited fluorescence compared with 47.9 ± 5.0% of vehicletreated, H 2 O 2 -exposed PAEC (Figure 4.3;n=24,p>0.25 Kuzkaya et al 2003;Landmesser et al 2003). Oxidation prevents NOS from transferring electrons to its physiologic substrate L-arginine (termed "uncoupling" of NOS) in static culture (Thomas et al 2002;Cai et al 2003b;Kuzkaya et al 2003;Landmesser et al 2003 (Coyle et al 2004). Therefore, we probed the effects of the combined contribution of NOS and NADPH oxidase to H 2 O 2 -induced increases in O 2 .-in PAEC using L-NAME and apocynin under shear conditions.…”

“…H 2 O 2 has also been found to stimulate increased eNOS expression, eNOS activity, and nitric oxide production in endothelial cells (Drummond et al 2000;Thomas et al 2002;Cai et al 2003b). Its ability to induce both nitric oxide (NO) and O 2 .-production makes H 2 O 2 a potent oxidative stimulus as it provides the components necessary for peroxynitrite formation (NO and O 2 .-interaction, (Beckman et al 1990;Pryor et al 1995).…”

Hydrogen peroxide stimulates the Ca2+-activated big-conductance K channels (BK) through cGMP signaling pathway in cultured human endothelial cells

“…Thus, results indicate that BK channels in cultured endothelial cells are stimulated by H 2 O 2 . It has been reported that H 2 O 2 increases nitric oxide (NO) production in endothelial cells in a previous study [12,13]. Because NO has been shown to stimulate BK activity in the cultured human endothelial cells in previous study [1], we examined whether the stimulatory effect of H 2 O 2 on BK channels was mediated by a NO-dependent mechanism.…”