title: Macrophage binding and the uptake of oxidized low density lipoprotein are regulated by intracellular protein phosphorylation.
abstract: The involvement of intracellular protein phosphorylation in macrophages in the binding and uptake of oxidized low density lipoprotein (oxLDL) was investigated. The treatment of fibronectin-unstimulated and stimulated mouse thioglycolate-induced macrophages with inhibitors of myosin light chain kinase, protein kinase C and protein tyrosine kinase resulted in decreased macrophage binding of oxLDL, macrophage foam cell formation, and whole intracellular protein phosphorylation. The treatment of fibronectin-unstimulated and stimulated macrophages with inhibitors of protein serine/threonine and tyrosine phosphatases caused enhanced macrophage binding of oxLDL, macrophage foam cell formation, and whole intracellular protein phosphorylation. Fibronectin, which stimulates macrophage activity, enhanced macrophage intracellular protein phosphorylation. Myosin light chain phosphorylation may be involved in the fibronectin stimulation of macrophages. Treatment of fibronectin-unstimulated and stimulated macrophages with thiophosphate, which forms thiophosphate esters of intracellular proteins that are not so susceptible to protein phosphatases, enhanced macrophage binding of oxLDL. The above results indicate that intracellular protein phosphorylation maintains and enhances macrophage binding and the uptake of oxLDL.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, 192-0392, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Beppu
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohishi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kasahara
authors.forename: Kengo
authors.initials: K
authors.lastname: Kizaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Inohana
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Kikugawa
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013864:Thioglycolates / Q000378:metabolism
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D005353:Fibronectins; D008077:Lipoproteins, LDL; D013864:Thioglycolates; C056218:ML 9; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; D010100:Oxygen