Nitric oxide attenuates hydrogen peroxide-mediated injury to porcine pulmonary artery endothelial cells

Abstract

To examine the role of nitric oxide (.NO) in vascular endothelial cell injury, cultured porcine pulmonary artery endothelial cells (PAEC) were treated with H2O2 (100-500 microM) for 30 min in the presence or absence of the .NO donors (+/-)S-nitroso-N-acetylpenicillamine (SNAP) or diethylamine nitric oxide (DEANO). H2O2 caused dose-dependent PAEC cytotoxicity detected 2 h after H2O2 treatment as the release of lactate dehydrogenase. SNAP (100 microM) and DEANO (100 microM) attenuated H2O2-induced cytotoxicity if present during H2O2 treatment. In contrast, restricting treatment with .NO donors to periods before (30 min) or after (2 h) incubation with H2O2 did not prevent PAEC injury. Furthermore, the .NO synthase inhibitor NG-nitro-L-arginine methyl ester (1 mM) sensitized PAEC to H2O2-induced injury. SNAP also attenuated H2O2-induced PAEC lipid peroxidation even if restricted to periods before or after exposure to H2O2. Thus, although .NO effectively attenuated H2O2-mediated PAEC lipid peroxidation and cytotoxicity, these effects were clearly dissociated, suggesting that the antiperoxidative effects of .NO are not sufficient to account for its cytoprotective properties.

Exosomes Derived from Human Pulmonary Artery Endothelial Cells Shift the Balance between Proliferation and Apoptosis of Smooth Muscle Cells

“…Therefore, we determined whether CF exosome release is altered in various injuring settings, including inflammation, hypoxia, and oxidative stress in cultured PAEC. To mimic these settings, LPS [17], hypoxic culture conditions [11], and H 2 O 2 [18] were used. We measured the total amount of proteins (concentrations) and protein expression levels of exosome markers CD63 in total exosomes released from the same number of PAEC after the treatment, as noted above.…”

Tumoricidal Activity of Endothelial Cells

“…Refs. 20, 21, 45, and 61), others have suggested that NO protects against reactive oxygen species (62,63). A plausible explanation for this apparent paradox is that both NO and H 2 O 2 can show very different effects depending on their concentrations.…”

Prenatal zinc supplementation to lipopolysaccharide infected female rats prevents neurochemical, behavioral and biochemical deficits produced in infants

“…O 2-and NO radicals, although they cannot react directly with GSH, can oxidize GSH after undergoing intracellular redox reactions NO can react with O 2-by radical-radical interaction forming peroxynitrite (ONOO -), thus clearing and scavenging O 2-in a diffusion limited rate. [61][62][63] ONOO -is a strong oxidizing agent, a reactive nitrogen species which oxidizes GSH rapidly to GSSG and depletes intracellular store of GSH. Similar results for glutathione system have been previously reported as decrease in GSH levels of maternal and fetal liver at 3 h, 6 h and 16 h after LPS injection to pregnant mice was observed.…”