Institute of Cardiovascular Disease, University of South China, Hengyang, China.
Acta Biochim Biophys Sin (Shanghai). 2010 Sep;42(9):635-45. doi: 10.1093/abbs/gmq070. Epub 2010 Aug 14.
It has been reported that oxidized low-density lipoprotein (Ox-LDL) can increase the expression of adipophilin. However, the detailed mechanisms are not fully understood. The aim of this study was to investigate the mechanism of Ox-LDL on adipophilin expression and the intracellular lipid droplet accumulation. A mouse macrophage-like cell line, RAW264.7, was used throughout, and it was found that Ox-LDL induced adipophilin expression in a dose-dependent manner. Moreover, Ox-LDL induced peroxisome proliferator-activated receptor-gamma (PPARgamma) expression and PPARgamma-specific inhibitor T0070907 abrogated Ox-LDL-induced adipophilin expression, but specific agonist GW1929 not. Furthermore, Ox-LDL induced phosphorylation of ERK1/2, and ERK1/2-specific inhibition by PD98059 suppressed the Ox-LDL-induced PPARgamma and adipophilin expression. The results showed that ERK1/2 or PPARgamma-specific inhibition decreased the amounts of intracellular lipid droplets. Meanwhile, the PPARgamma-specific agonist increased intracellular lipid droplets. These results suggested that Ox-LDL-induced increase in adipophilin level via ERK1/2 activation is one of the mechanisms of inducing greater amounts of intracellular lipid droplets in RAW264.7 cells, which indicated that adipophilin is involved in atherosclerotic progression.
据报道，氧化型低密度脂蛋白（Ox-LDL）可以增加脂联素的表达。然而，其详细机制尚不完全清楚。本研究旨在探讨 Ox-LDL 对脂联素表达和细胞内脂滴积累的作用机制。本研究采用小鼠巨噬细胞样细胞系 RAW264.7，结果发现 Ox-LDL 呈剂量依赖性诱导脂联素表达。此外，Ox-LDL 诱导过氧化物酶体增殖物激活受体-γ（PPARγ）表达，PPARγ 特异性抑制剂 T0070907 可阻断 Ox-LDL 诱导的脂联素表达，但特异性激动剂 GW1929 则无此作用。进一步研究发现，Ox-LDL 诱导 ERK1/2 的磷酸化，ERK1/2 的特异性抑制剂 PD98059 抑制 Ox-LDL 诱导的 PPARγ 和脂联素表达。结果表明，ERK1/2 或 PPARγ 的特异性抑制减少了细胞内脂滴的数量。同时，PPARγ 的特异性激动剂增加了细胞内脂滴。这些结果表明，Ox-LDL 通过激活 ERK1/2 诱导脂联素水平增加是 RAW264.7 细胞中诱导更多细胞内脂滴的机制之一，提示脂联素参与动脉粥样硬化的进展。
