title: Activation of cellular chemotactic responses to chemokines coupled with oxidation of plasma membrane proteins by lysyl oxidase.
abstract: Lysyl oxidase (LOX) is a potent chemokine inducing the migration of varied cell types. Here we demonstrate that inhibition of cellular LOX activity by preincubation of vascular smooth muscle cells (VSMC) with β-aminopropionitrile (BAPN), the irreversible inhibitor of LOX activity, resulted in the marked suppression of the chemotactic response and sensitivity of these cells toward LOX and toward PDGF-BB. Plasma membranes purified from VSMC not previously exposed to BAPN contained a group of oxidized plasma membrane proteins, including the PDGF receptor, PDGFR-β. The oxidation of this receptor and other membrane proteins was largely prevented in cells preincubated with BAPN. Addition of purified LOX to BAPN-free cells, which had been previously exposed to BAPN, restored the profile of oxidized proteins towards that of control cells. The high affinity and capacity for the binding of PDGF-BB by cells was significantly diminished when compared with cells in which oxidation by LOX was prevented by BAPN. The chemotactic responses of LOX knock-out mouse embryonic fibroblasts mirrored those obtained with VSMC treated with BAPN. These novel findings suggest that LOX activity is essential to generate optimal chemotactic sensitivity of cells to chemoattractants by oxidizing specific cell surface proteins, such as PDGFR-β.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Héctor A
authors.initials: HA
authors.lastname: Lucero
authors.forename: Joni M
authors.initials: JM
authors.lastname: Mäki
authors.forename: Herbert M
authors.initials: HM
authors.lastname: Kagan
mesh_terms: D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology* / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism / Q000502:physiology
chemical_list: D018925:Chemokines; D008565:Membrane Proteins; D008249:Protein-Lysine 6-Oxidase; D020797:Receptor, Platelet-Derived Growth Factor beta