Beppu Masatoshi, Ohishi Kenji, Kasahara Masaaki, Kizaki Kengo, Inohana Yuko, Kikugawa Kiyomi
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, 192-0392, Japan.
J Biochem. 2002 Apr;131(4):547-55. doi: 10.1093/oxfordjournals.jbchem.a003133.
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.
研究了细胞内蛋白磷酸化在巨噬细胞结合和摄取氧化低密度脂蛋白（oxLDL）中的作用。用肌球蛋白轻链激酶、蛋白激酶C和蛋白酪氨酸激酶抑制剂处理未受纤连蛋白刺激和受刺激的小鼠巯基乙酸诱导的巨噬细胞，导致巨噬细胞对oxLDL的结合减少、巨噬细胞泡沫细胞形成以及细胞内整体蛋白磷酸化降低。用蛋白丝氨酸/苏氨酸和酪氨酸磷酸酶抑制剂处理未受纤连蛋白刺激和受刺激的巨噬细胞，导致巨噬细胞对oxLDL的结合增强、巨噬细胞泡沫细胞形成以及细胞内整体蛋白磷酸化增强。刺激巨噬细胞活性的纤连蛋白增强了巨噬细胞内蛋白磷酸化。肌球蛋白轻链磷酸化可能参与了纤连蛋白对巨噬细胞的刺激作用。用硫代磷酸盐处理未受纤连蛋白刺激和受刺激的巨噬细胞，硫代磷酸盐会形成不易被蛋白磷酸酶作用的细胞内蛋白硫代磷酸酯，增强了巨噬细胞对oxLDL的结合。上述结果表明，细胞内蛋白磷酸化维持并增强了巨噬细胞对oxLDL的结合和摄取。
