title: Hydrogen peroxide signaling mediator in the activation of p38 MAPK in vascular endothelial cells.
abstract: Substantial evidence suggests that a transient increase of hydrogen peroxide (H2O2) behaves as an intracellular messenger able to trigger the activation of different signaling pathways. These include phosphatases, protein kinases, and transcription factors among others; however, most of the studies have been performed using supraphysiological levels of H2O2. Reactive oxygen species (ROS) generation occurs under physiological conditions and different extracellular stimuli including cytokines, growth factors, and shear stress are able to produce both low levels of superoxide anion and H2O2. Here, we explore the redox-dependent activation of key signaling pathways induced by shear stress. We demonstrate that laminar shear stress (LSS) rapidly promotes a transient generation of H2O2 that is necessary for the activation of the stress-activated protein kinase p38 MAPK. We describe p38 MAPK as an early redox sensor in LSS. Our studies show that it is essential for the activation of endothelial nitric oxide synthase, the subsequent nitric oxide generation, and the protection of endothelial function.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bretón-Romero
authors.forename: Santiago
authors.initials: S
authors.lastname: Lamas
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000737:chemistry; D005949:Glucose Oxidase / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D013481:Superoxides / Q000032:analysis / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D052250:Nitric Oxide Synthase Type III; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: Endothelium; Laminar shear stress; Nitric oxide; Reactive oxygen species; p38 MAPK