IGF-1R、p-ERK参与低密度脂蛋白诱导小鼠腹腔巨噬细胞存活(英文)

IGF-1R, p-ERK is involved in LDLs-induced mouse peritoneal macrophage survival*

目的 :研究低密度脂蛋白对小鼠腹腔巨噬细胞胰岛素样生长因子 - 1受体 (IGF - 1R)、磷酸化细胞外信号调节激酶 (p -ERK)、Bcl- 2和Bax表达的影响 ,从而探讨低密度脂蛋白诱导巨噬细胞存活的机理。方法 :应用免疫细胞化学和Westernblotting方法 ,检测低密度脂蛋白对小鼠腹腔巨噬细胞IGF - 1R、p -ERK、Bcl- 2和Bax表达的影响。结果 :氧化型低密度脂蛋白 (oxLDL)以剂量和时间依赖的方式增加IGF - 1R的表达。oxLDL刺激 5min后 ,p -ERK表达最高。oxLDL诱导ERK从细胞浆内转至胞核内。给予IGF - 1R抗体后 ,oxLDL诱导p -ERK表达降低 ,并且ERK转核过程消失。oxLDL以浓度和时间依赖的方式增加Bcl- 2的表达 ,降低Bax的表达。给予ERK抑制剂PD980 5 9后 ,oxLDL诱导Bcl- 2表达降低 ,而Bax蛋白表达明显增高。自然型LDL对这 4种蛋白的表达无明显影响。结论 :oxLDL诱导巨噬细胞存活至少是通过增加IGF - 1R的表达及ERK磷酸化实现的 ,并且可能存在其他的途径参与oxLDL诱导巨噬细胞存活。

AIM: To study the effects of low density lipoproteins (LDLs) on insulin-like growth factor-1 receptor (IGF-1R), phosphorylated extracellular signal-regulated kinase (p-ERK), Bcl-2 and Bax protein expression in mouse peritoneal macrophages (MPMs). METHODS: Using the methods of immunocytochemistry and Western blotting, the expression of IGF-1R, p-ERK, Bcl-2 and Bax protein in MPMs treated with LDLs, anti-IGF-1R antibody (α-IR-3) or ERK inhibitor (PD98059) were detected. RESULTS: oxLDL significantly increased the IGF-1R protein expression in a dose and time-dependent manner. P-ERK protein expression induced by oxLDL peaked at 5 min. Moreover, oxLDL could induced ERK translocation from cytoplasm to nuclear. When given α-IR-3, p-ERK protein expression was significantly inhibited, and ERK translocation disappeared. oxLDL increased Bcl-2 protein expression and reduced Bax expression in a dose and time-dependent manner. When given PD98059, Bcl-2 and Bax protein expression induced by oxLDL altered significantly. Native LDL had no significant effect on the expression of these four proteins. CONCLUSIONS: oxLDL may promote cultured MPMs survival at least by enhancing IGF-1R expression and ERK phosphorylation, and there may be many pathways involved in MPMs survival induced by oxLDL, Whereas native LDL had no effects on culture MPMs.