title: Hydroxyalkenals and oxidized phospholipids modulation of endothelial cytoskeleton, focal adhesion and adherens junction proteins in regulating endothelial barrier function.
abstract: Lipid peroxidation of polyunsaturated fatty acids generates bioactive aldehydes, which exhibit pro- and anti-inflammatory effects in cells and tissues. Accumulating evidence indicates that 4-hydroxynonenal (4-HNE), a major aldehyde derived from lipid peroxidation of n-6 polyunsaturated fatty acids trigger signals that modulates focal adhesion and adherens junction proteins thereby inducing endothelial barrier dysfunction. Similarly, oxidized phospholipids (Ox-PLs) generated by lipid peroxidation of phospholipids with polyunsaturated fatty acids have been implicated in atherogenesis, inflammation and gene expression. Interestingly, physiological concentration of Ox-PLs is anti-inflammatory and protect against endotoxin- and ventilator-associated acute lung injury. Thus, excess generation of bioactive hydroxyalkenals and Ox-PLs during oxidative stress contributes to pathophysiology of various diseases by modulating signaling pathways that regulate pro- and anti-inflammatory responses and barrier regulation. This review summarizes the role of 4-HNE and Ox-PLs affecting cell signaling pathways and endothelial barrier dysfunction through modulation of the activities of proteins/enzymes by Michael adducts formation, enhancing the level of protein tyrosine phosphorylation of the target proteins, and by reorganization of cytoskeletal, focal adhesion, and adherens junction proteins. A better understanding of molecular mechanisms of hydroxyalkenals- and Ox-PLs-mediated pro-and anti-inflammatory responses and barrier function may lead to development of novel therapies to ameliorate oxidative stress related cardio-pulmonary disorders.
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Usatyuk
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability; D003599:Cytoskeleton / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010743:Phospholipids / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000447:Aldehydes; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D010743:Phospholipids; C027576:4-hydroxy-2-nonenal