Phosphatidylethanolamine binding protein 1 in vacular endothelial cell autophagy and atherosclerosis
Phosphatidylethanolamine binding protein 1 in vacular endothelial cell autophagy and atherosclerosis
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DOI：
10.1113/jphysiol.2013.262667
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发表时间：
2013-10-15
影响因子：
5.5
通讯作者：
Miao, JunYing
中科院分区：
文献类型：
--
作者：
Wang, Li;Li, HaiYing;Miao, JunYing
我们以前发现磷脂酰胆碱特异性磷脂酶C（PC-PLC）是动脉粥样硬化的关键诱导因子，并可能负性调节人脐静脉内皮细胞（HUVEC）的自噬。为了进一步研究PC-PLC的作用机制，我们通过质谱（MS，MALDI-TOF/TOF）初步鉴定了磷脂酰乙醇胺结合蛋白1（PEBP 1）作为PC-PLC的结合伴侣。我们发现PEBP 1正调控HUVECs中的PC-PLC活性，并且其抑制剂D 609抑制PC-PLC显著抑制PEBP 1的表达。此外，PC-PLC和PEBP 1均不依赖于哺乳动物雷帕霉素靶蛋白（mTOR）负调控HUVEC自噬。此外，PEBP 1水平在动脉粥样硬化的发展过程中升高，而D 609显著降低apoE（-/-）小鼠中上调的PEBP 1水平。
We previously found that phosphatidylcholine-specific phospholipase C (PC-PLC) was a key inducing element of atherosclerosis, and might negatively regulate human umbilical vein endothelial cell (HUVEC) autophagy. To further investigate the mechanism of PC-PLC action, we initially identified phosphatidylethanolamine binding protein 1 (PEBP1) as a binding partner of PC-PLC by using mass spectrometry (MS, MALDI-TOF/TOF). We found that PEBP1 positively regulated PC-PLC activity in HUVECs, and inhibition of PC-PLC by its inhibitor D609 suppressed PEBP1 expression dramatically. Moreover, both PC-PLC and PEBP1 negatively regulated HUVEC autophagy independently of mammalian target of rapamycin (mTOR). Furthermore, the PEBP1 level was elevated during the development of atherosclerosis, while D609 significantly decreased the upregulated PEBP1 level in apoE(-/-) mice.