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Lipoproteins and mitogen-activated protein kinase signaling: a role in atherogenesis?

机译:脂蛋白和丝裂原激活的蛋白激酶信号传导:在动脉粥样硬化中的作用?

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PURPOSE OF REVIEW: Lipoproteins play a critical role in the development of atherosclerosis, which might result partly from their capacity to induce specific intracellular signaling pathways. The goal of this review is to summarize the signaling properties of lipoproteins, in particular, their capacity to induce activation of mitogen-activated protein kinase pathways and the resulting modulation of cellular responses in blood vessel cells. RECENT FINDINGS: Lipoproteins activate the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways in all blood vessel cell types. This may require lipoprotein docking to scavenger receptor B1, allowing transfer of cholesterol and sphingosine-1-phosphate to plasma membranes. Subsequent propagation of the signals probably requires the stimulation of G protein-coupled receptors, followed by the transactivation of receptor tyrosine kinases. Lipoprotein-induced extracellular signal-regulated kinase activity favors cell proliferation, whereas lipoprotein-induced p38 mitogen-activated protein kinase activity leads to cell hyperplasia and promotes cell migration. Some signaling pathways and cellular effects induced by lipoproteins have been observed in atherosclerotic plaques and therefore represent potential targets for the development of anti-atherosclerotic drugs. SUMMARY: The main blood vessel cell types have the capacity to activate protein kinase pathways in the presence of lipoproteins. This induces cell proliferation, hyperplasia and migration, known to be dysregulated in atherosclerotic lesions.
机译:审查目的:脂蛋白在动脉粥样硬化的发展中起关键作用,这可能部分是由于它们诱导特定的细胞内信号通路的能力所致。这篇综述的目的是概述脂蛋白的信号传导特性,特别是其诱导丝裂原活化的蛋白激酶途径活化的能力以及对血管细胞中细胞应答的调节。最近的发现:脂蛋白激活所有血管细胞类型中的细胞外信号调节激酶和p38丝裂原激活的蛋白激酶途径。这可能需要脂蛋白对接清除剂受体B1,使胆固醇和1鞘氨醇磷酸酯转移到质膜上。信号的后续传播可能需要刺激G蛋白偶联受体,然后激活受体酪氨酸激酶。脂蛋白诱导的细胞外信号调节激酶活性促进细胞增殖,而脂蛋白诱导的p38促分裂原活化蛋白激酶活性导致细胞增生并促进细胞迁移。在动脉粥样硬化斑块中已经观察到由脂蛋白诱导的某些信号传导途径和细胞作用,因此代表了抗动脉粥样硬化药物开发的潜在目标。摘要:主要的血管细胞类型具有在存在脂蛋白的情况下激活蛋白激酶途径的能力。这会诱导细胞增殖,增生和迁移,已知在动脉粥样硬化病变中失调。

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