title: Phospholipid scramblase 1 is required for β2-glycoprotein I binding in hypoxia and reoxygenation-induced endothelial inflammation.
abstract: Multiple pathologic conditions, including hemorrhage, tumor angiogenesis, and ischemia-reperfusion events, will result in hypoxia and subsequent reperfusion. Previous studies have analyzed the lipid changes within whole tissues and indicated that ischemia-reperfusion altered tissue and cellular phospholipids. Using an in vitro cell culture model of hypoxia and reoxygenation, we examined the endothelial lipid changes. We hypothesized that phospholipid scramblase 1, a protein that regulates bilayer asymmetry, is involved in altering the phospholipids of endothelial cells during hypoxia, a component of ischemia, leading to β2-glycoprotein I and IgM binding and subsequent lipid-mediated, inflammatory responses. We have completed the first comprehensive study of steady-state phospholipid scramblase 1 mRNA levels, protein expression, and activity under conditions of hypoxia and reoxygenation. Phospholipid scramblase 1 regulates phosphatidylserine exposure in response to oxygen stress, leading to β2-glycoprotein I and IgM binding and lipid-mediated, inflammatory responses.
authors.affiliation: Division of Biology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Emily Archer
authors.initials: EA
authors.lastname: Slone
authors.affiliation: Division of Biology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Pope
authors.affiliation: Division of Biology, Kansas State University, Manhattan, Kansas, USA sdflemin@ksu.edu.
authors.forename: Sherry D
authors.initials: SD
authors.lastname: Fleming
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014657:Vasculitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053482:beta 2-Glycoprotein I / Q000235:genetics / Q000378:metabolism*
chemical_list: D007075:Immunoglobulin M; D049294:Phospholipid Transfer Proteins; C493426:Plscr1 protein, mouse; D053482:beta 2-Glycoprotein I
keywords: Ischemia and reperfusion; apolipoprotein H; eicosanoids