1.NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets.
Dennis KE1, Aschner JL, Milatovic D, Schmidt JW, Aschner M, Kaplowitz MR, Zhang Y, Fike CD. Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L596-607. doi: 10.1152/ajplung.90568.2008. Epub 2009 Jul 10.
Recently, we reported that reactive oxygen species (ROS) generated by NADPH oxidase (NOX) contribute to aberrant responses in pulmonary resistance arteries (PRAs) of piglets exposed to 3 days of hypoxia (Am J Physiol Lung Cell Mol Physiol 295: L881-L888, 2008). An objective of the present study was to determine whether NOX-derived ROS also contribute to altered PRA responses at a more advanced stage of pulmonary hypertension, after 10 days of hypoxia. We further wished to advance knowledge about the specific NOX and antioxidant enzymes that are altered at early and later stages of pulmonary hypertension. Piglets were raised in room air (control) or hypoxia for 3 or 10 days. Using a cannulated artery technique, we found that treatments with agents that inhibit NOX (apocynin) or remove ROS [an SOD mimetic (M40403) + polyethylene glycol-catalase] diminished responses to ACh in PRAs from piglets exposed to 10 days of hypoxia. Western blot analysis showed an increase in expression of NOX1 and the membrane fraction of p67phox.
2.Anesthetic-induced oxidative stress and potential protection.
Wang C1, Zhang X, Liu F, Paule MG, Slikker W Jr. ScientificWorldJournal. 2010 Jul 20;10:1473-82. doi: 10.1100/tsw.2010.118.
Prolonged exposure of developing mammals to general anesthetics affects the N-methyl-D-aspartate (NMDA)-type glutamate or gamma-aminobutyric acid (GABA) receptor systems and enhances neuronal toxicity. Stimulation of immature neurons by NMDA antagonists or GABA agonists is thought to increase overall nervous system excitability and may contribute to abnormal neuronal cell death during development. Although the precise mechanisms by which NMDA antagonists or GABA agonists cause neuronal cell death are still not completely understood, up-regulation of the NMDA receptor subunit NR1 may be an initiative factor in neuronal cell death. It is increasingly apparent that mitochondria lie at the center of the cell death regulation process. Evidence for the role of oxidative stress in anesthetic-induced neurotoxicity has been generated in studies that apply oxidative stress blockers. Prevention of neuronal death by catalase and superoxide dismutase in vitro, or by M40403 (superoxide dismutase mimetic) in vivo, supports the contention that the involvement of reactive oxygen species (ROS) and the nature of neuronal cell death in rodents is mainly apoptotic.
3.Nox4 mediates the expression of plasminogen activator inhibitor-1 via p38 MAPK pathway in cultured human endothelial cells.
Jaulmes A1, Sansilvestri-Morel P, Rolland-Valognes G, Bernhardt F, Gaertner R, Lockhart BP, Cordi A, Wierzbicki M, Rupin A, Verbeuren TJ. Thromb Res. 2009 Sep;124(4):439-46. doi: 10.1016/j.thromres.2009.05.018. Epub 2009 Jun 21.
INTRODUCTION: Plasminogen Activator Inhibitor-1 (PAI-1) is the most potent endogenous inhibitor of fibrinolysis which is implicated in the pathogenesis of myocardial infarction and metabolic syndrome. The formation of reactive oxygen species (ROS) plays an important role in the pathology of vascular disorders and has been shown to increase PAI-1 expression by endothelial cells. Growing evidence indicates that NADPH oxidase and in particular the constitutively active Nox4-p22(phox) complexes are major sources of ROS in endothelial cells. The aim of the present study was to characterize the role of NADPH oxidase and in particular Nox4 in the regulation of PAI-1 expression in cultured Human Umbilical Venous Endothelial Cells (HUVECs).