Luan Yingjun, Griffiths Helen R
Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
Arch Biochem Biophys. 2006 Jun 1;450(1):89-99. doi: 10.1016/j.abb.2006.03.016. Epub 2006 Mar 29.
Oxidised LDL accumulates in macrophages following scavenger receptor (SR) uptake. The expression of the SR, CD36, is increased by oxidised LDL. The signalling molecule, ceramide, can modulate intracellular peroxides and increase lipid peroxidation. Ceramide also accumulates in atherosclerotic plaques. Thus, we have examined whether ceramide can modulate CD36 expression and function in human monocyte/macrophages. Addition of synthetic short chain ceramides or the action of sphingomyelinase to generate physiological long chain ceramides in situ caused significant reductions in CD36 expression by monocytes/macrophages which was not due to inhibition of mRNA expression. Inhibition of proteasomal degradation using lactacystin had no effect on CD36 expression, however, flow cytometric analysis of permeabilised cells suggested an intracellular trafficking blockade. Ceramide treated monocytes/macrophages showed dose dependent reduction in oxidised LDL uptake. Taken together, it is suggested that ceramide blocks the transport of CD36 to the membrane of monocytes/macrophages, thereby preventing uptake of oxidised LDL.
氧化型低密度脂蛋白（ox-LDL）在通过清道夫受体（SR）摄取后会在巨噬细胞中蓄积。SR（CD36）的表达会因氧化型低密度脂蛋白而增加。信号分子神经酰胺可调节细胞内过氧化物并增加脂质过氧化。神经酰胺也会在动脉粥样硬化斑块中蓄积。因此，我们研究了神经酰胺是否能调节人单核细胞/巨噬细胞中CD36的表达和功能。添加合成短链神经酰胺或鞘磷脂酶原位生成生理性长链神经酰胺，会导致单核细胞/巨噬细胞中CD36的表达显著降低，这并非由于mRNA表达受到抑制。使用乳胞素抑制蛋白酶体降解对CD36表达没有影响，然而，对通透细胞的流式细胞术分析表明存在细胞内运输阻滞。经神经酰胺处理的单核细胞/巨噬细胞对氧化型低密度脂蛋白的摄取呈剂量依赖性降低。综上所述，提示神经酰胺阻断了CD36向单核细胞/巨噬细胞膜的转运，从而阻止了氧化型低密度脂蛋白的摄取。
