TY - CHAP
T1 - Chapter 8 Reactive Oxygen Species and Endothelial Permeability
AU - Ushio-Fukai, Masuko
AU - Frey, Randall S.
AU - Fukai, Tohru
AU - Malik, Asrar B.
N1 - Funding Information:
This work as supported by NIH ROI HL077524 (to M.U.-F), AHA Grant-in-Aid 0555308B (to M.U.-F) and 0755805Z (to M.U.-F), and NIH HL60678 (to A.B.M), NIH ROI HL45638 (to A.B.M), NIH POI HL077806 (to A.B.M) T32 HL 07829 (to A.B.M), T32GM070388 (to A.B.M), ROI HL090152 (to A.B.M).
PY - 2008
Y1 - 2008
N2 - Alterations in endothelial permeability are a defining feature of diverse processes including arteriosclerosis, inflammation, ischemia/reperfusion injury, angiogenesis, pulmonary edema in acute lung injury and adult respiratory distress syndrome. Endothelial monolayer permeability increases as a result of both disruption of endothelial cell-cell contacts and EC contraction. Disruption of endothelial cell-cell junctions occurs concomitantly with the redistribution and tyrosine phosphorylation of the VE-cadherin-containing adherens junction (AJ) protein complexes. Little is known about mechanisms of how endothelial permeability is regulated. Reactive oxygen species (ROS) including superoxide (O2-) and hydrogen peroxide (H2O2) generated by activated polymorphonuclear leukocyte (PMNs) and endothelial cells (ECs) impair endothelial barrier integrity by promoting loss of cell-cell adhesions and reorganization of actin cytoskeleton. These responses are involved in promoting transendothelial migration of PMNs and endothelial permeability. Major source of ROS in PMNs and ECs is NADPH oxidase. Phagocyte NADPH oxidase consists of membrane-bound gp91phox and p22hox as well as cytosolic components such as p47phox, p67phox and small GTPase Rac. Recently, several novel homologues of gp91phox (Nox2) of NADPH oxidase (Nox) have been cloned in non-phagocytic cells. In ECs Nox1, Nox2, Nox4 and Nox5 are functionally expressed. NADPH oxidase in ECs is activated by inflammatory cytokines, thrombogenic agents, growth factors, G-protein coupled receptor agonists and shear stress. ROS derived from NADPH oxidase function as signaling molecules to activate various redox signaling pathways through modulating activity of kinases and phosphatases, which may contribute to increase in endothelial permeability. Understanding mechanisms by which ROS regulate endothelial permeability is important for the development of novel therapeutic approaches against various diseases such as inflammation, atherogenesis and acute lung injury.
AB - Alterations in endothelial permeability are a defining feature of diverse processes including arteriosclerosis, inflammation, ischemia/reperfusion injury, angiogenesis, pulmonary edema in acute lung injury and adult respiratory distress syndrome. Endothelial monolayer permeability increases as a result of both disruption of endothelial cell-cell contacts and EC contraction. Disruption of endothelial cell-cell junctions occurs concomitantly with the redistribution and tyrosine phosphorylation of the VE-cadherin-containing adherens junction (AJ) protein complexes. Little is known about mechanisms of how endothelial permeability is regulated. Reactive oxygen species (ROS) including superoxide (O2-) and hydrogen peroxide (H2O2) generated by activated polymorphonuclear leukocyte (PMNs) and endothelial cells (ECs) impair endothelial barrier integrity by promoting loss of cell-cell adhesions and reorganization of actin cytoskeleton. These responses are involved in promoting transendothelial migration of PMNs and endothelial permeability. Major source of ROS in PMNs and ECs is NADPH oxidase. Phagocyte NADPH oxidase consists of membrane-bound gp91phox and p22hox as well as cytosolic components such as p47phox, p67phox and small GTPase Rac. Recently, several novel homologues of gp91phox (Nox2) of NADPH oxidase (Nox) have been cloned in non-phagocytic cells. In ECs Nox1, Nox2, Nox4 and Nox5 are functionally expressed. NADPH oxidase in ECs is activated by inflammatory cytokines, thrombogenic agents, growth factors, G-protein coupled receptor agonists and shear stress. ROS derived from NADPH oxidase function as signaling molecules to activate various redox signaling pathways through modulating activity of kinases and phosphatases, which may contribute to increase in endothelial permeability. Understanding mechanisms by which ROS regulate endothelial permeability is important for the development of novel therapeutic approaches against various diseases such as inflammation, atherogenesis and acute lung injury.
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U2 - 10.1016/S1063-5823(08)00208-1
DO - 10.1016/S1063-5823(08)00208-1
M3 - Chapter
AN - SCOPUS:48649102134
SN - 9780123738790
T3 - Current Topics in Membranes
SP - 147
EP - 189
BT - Free Radical Effects on Membranes
A2 - Matalon, Sadis
ER -