Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apolipoproteins E / genetics
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Atherosclerosis / metabolism*
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Autophagy*
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Bridged-Ring Compounds / pharmacology
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Human Umbilical Vein Endothelial Cells / metabolism*
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Human Umbilical Vein Endothelial Cells / physiology
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Humans
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Mice
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Mice, Inbred C57BL
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Norbornanes
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Phosphatidylethanolamine Binding Protein / genetics
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Phosphatidylethanolamine Binding Protein / metabolism*
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Protein Binding
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TOR Serine-Threonine Kinases / metabolism
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Thiocarbamates
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Thiones / pharmacology
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Type C Phospholipases / antagonists & inhibitors
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Type C Phospholipases / metabolism
Substances
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Apolipoproteins E
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Bridged-Ring Compounds
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Norbornanes
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PEBP1 protein, human
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Phosphatidylethanolamine Binding Protein
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Thiocarbamates
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Thiones
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tricyclodecane-9-yl-xanthogenate
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TOR Serine-Threonine Kinases
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Type C Phospholipases
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phosphatidylcholine-specific phospholipase C