Nicholson A C, Febbraio M, Han J, Silverstein R L, Hajjar D P
Center of Vascular Biology, Cornell University Medical College, New York, New York, USA.
Ann N Y Acad Sci. 2000 May;902:128-31; discussion 131-3.
CD36, an 88 kD transmembrane glycoprotein, is an important receptor for oxidized lipoproteins. Unlike the LDL receptor, expression of CD36 is upregulated by this pro-atherogenic particle, and binding and uptake perpetuates a cycle of lipid accumulation and receptor expression. This effect is, in part, mediated by the transcription factor, peroxisome proliferator activated receptor-gamma (PPAR gamma), and its ligands. We have found that specific inhibitors of protein kinase C (PKC) reduce basal mRNA expression of CD36 and block induction of CD36 mRNA and protein by oxidized LDL (OxLDL) and a PPAR gamma ligand. In addition, PKC inhibitors block both PPAR gamma mRNA and protein expression. These results suggest that activation of CD36 gene expression by OxLDL involves activation and translocation of PKC with subsequent PPAR gamma activation. More recently, we have generated a mouse null for CD36, and crossed it with the atherogenic Apo E null strain. Evaluation of lesion development in these animals will allow us to assess the in vivo contribution of CD36 to the pathogenesis of atherosclerosis.
CD36是一种88千道尔顿的跨膜糖蛋白，是氧化型脂蛋白的重要受体。与低密度脂蛋白（LDL）受体不同，CD36的表达会被这种促动脉粥样硬化颗粒上调，其结合和摄取会使脂质积累和受体表达的循环持续下去。这种效应部分由转录因子过氧化物酶体增殖物激活受体γ（PPARγ）及其配体介导。我们发现蛋白激酶C（PKC）的特异性抑制剂可降低CD36的基础mRNA表达，并阻断氧化型低密度脂蛋白（OxLDL）和PPARγ配体对CD36 mRNA和蛋白的诱导。此外，PKC抑制剂可同时阻断PPARγ mRNA和蛋白表达。这些结果表明，OxLDL对CD36基因表达的激活涉及PKC的激活和转位以及随后的PPARγ激活。最近，我们培育出了CD36基因敲除小鼠，并将其与致动脉粥样硬化的载脂蛋白E基因敲除品系杂交。对这些动物病变发展的评估将使我们能够评估CD36在动脉粥样硬化发病机制中的体内作用。
