Oxidized LDL and lysophosphatidylcholine stimulate plasminogen activator inhibitor-1 expression through reactive oxygen species generation and ERK1/2 activation in 3T3-L1 adipocytes
Oxidized LDL and lysophosphatidylcholine stimulate plasminogen activator inhibitor-1 expression through reactive oxygen species generation and ERK1/2 activation in 3T3-L1 adipocytes
复制标题
DOI：
10.1016/j.bbalip.2010.11.011
复制
发表时间：
2011-03-01
影响因子：
4.8
通讯作者：
Nakayama, Hitoshi
中科院分区：
文献类型：
--
作者：
Kuniyasu, Akihiko;Tokunaga, Mariko;Nakayama, Hitoshi
纤溶酶原激活物抑制剂-1（派-1）由脂肪组织分泌，被认为是动脉粥样硬化和胰岛素抵抗的危险因素。在这里，我们报告的第一次，派-1的表达增强氧化低密度脂蛋白（OxLDL）和其脂质成分溶血磷脂酰胆碱（LPC）在小鼠3 T3-L1脂肪细胞。在完全分化的3 T3-L1细胞中，OxLDL处理以剂量和时间依赖性方式增加派-1的mRNA表达和蛋白分泌，而天然LDL没有影响。添加抗CD 36抗体抑制OxLDL刺激的派-1表达50%，表明脂肪来源的CD 36贡献了OxLDL刺激的派-1表达的大约一半。药理学实验表明，OxLDL刺激的派-1表达增强是通过活性氧簇（ROS）的产生和细胞外信号调节激酶1/2的磷酸化介导的。此外，LPC，OxLDL的主要脂质成分，负责增强派-1的表达，因为磷脂酶A（2）处理的乙酰LDL，产生LPC，强烈刺激派-1的表达，而乙酰LDL本身没有这种活性。这些数据表明，摄取OxLDL，特别是其脂质成分LPC进入脂肪细胞触发异常ROS介导的派-1表达，这可能涉及代谢综合征的发病机制。(C)出版社：Elsevier B. V.
Plasminogen activator inhibitor-1 (PAI-1) is secreted from adipose tissue and is considered to be a risk factor for both atherosclerosis and insulin resistance. Here we report for the first time that PAI-1 expression is enhanced by oxidized low-density lipoprotein (OxLDL) and its lipid component lysophosphatidylcholine (LPC) in mouse 3T3-L1 adipocytes. In fully differentiated 3T3-L1 cells, OxLDL treatment increased the mRNA expression and protein secretion of PAI-1 in a dose- and time-dependent manner, whereas native LDL had no effect The addition of an anti-CD36 antibody suppressed OxLDL-stimulated PAI-1 expression by 50%, suggesting that adipose-derived CD36 contributes to roughly half of the PAI-1 expression stimulated by OxLDL In addition, pharmacological experiments showed that the OxLDL-stimulated enhancement in PAI-1 expression was mediated through the generation of reactive oxygen species (ROS) and phosphorylation of extracellular signal-regulated kinase 1/2. Furthermore, LPC, a major lipid component of OxLDL, was responsible for the enhanced expression of PAI-1 as phospholipase A(2)-treated acetyl LDL, which generates LPC, strongly stimulated PAI-1 expression, whereas acetyl LDL itself had no such activity. These data demonstrate that the uptake of OxLDL and, in particular, its lipid component LPC into adipocytes triggers aberrant ROS-mediated PAI-1 expression, which may be involved in the pathogenesis of metabolic syndrome. (C) 2010 Published by Elsevier B.V.