Low-density lipoprotein inhibits secretion of phospholipid transfer protein in human trophoblastic BeWo cells.
Human plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. In this study, we investigated the effects of lipoproteins on the secretion of PLTP in cultured BeWo choriocarcinoma cells. Low-density lipoproteins (LDLs) decreased PLTP secretion in a dose- and time-dependent manner, whereas very low density lipoproteins and high-density lipoproteins (HDLs) had little effect. LDL suppression of PLTP secretion was not altered by the inhibition of both LDL receptor and LDL receptor-related protein with receptor-associated protein. Mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor, U0126, could abolish the LDL-mediated inhibition of PLTP secretion. Furthermore, LDL, but not HDL, could stimulate the expression of MAPK phosphatase-1 (MKP-1) in BeWo cells that resulted in the inactivation of p44/p42 extracellular signal-regulated kinase (ERK) 1 and 2, the family members of MAPKs. These results support the conclusion that LDL-mediated suppression of PLTP secretion in BeWo cells is through a LDL receptor-independent MAPK signaling pathway.
Tu
An-Yue
AY
Department of Medicine, Northwest Lipid Research Laboratories, Northwest Lipid Research Clinic, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, 2121 N 35th Street, Seattle, WA 98103, USA. aytu@u.washington.edu.
Cheung
Marian C
MC
Zhu
Xiaodong
X
Knopp
Robert H
RH
Albers
John J
JJ
D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D049294:Phospholipid Transfer Proteins; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000473:pathology*
D002070:Butadienes; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008565:Membrane Proteins; D009570:Nitriles; D049294:Phospholipid Transfer Proteins; C113580:U 0126; D020930:MAP Kinase Kinase Kinases