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.
TallAR, JiangX-C, LuoY, SilverD. Lipid transfer proteins, HDL metabolism, and atherogenesis. Arterioscler Thromb Vasc Biol20: 11851188, 2000.
2.
van TolA. Phospholipid transfer protein. Curr Opin Lipidol13: 135139, 2002.
3.
OramJF, WolfbauerG, VaughanAM, TangC, AlbersJJ. Phospholipid transfer protein interacts with and stabilizes ATP-binding cassette transporter Al and enhances cholesterol efflux from cells. J Biol Chem278: 5237952385, 2003.
4.
TollefsonJH, RavnikS, AlbersJJ. Isolation and characterization of a phospholipid transfer protein (LTP-II) from human plasma. J Lipid Res29: 15931602, 1988.
5.
TallAR, KrumholzS, OlivecronaT, DeckelbaumRJ. Plasma phospholipid transfer protein enhances transfer and exchange of phospholipids between very low density lipoproteins and high density lipoproteins during lipolysis. J Lipid Res26: 842851, 1985.
6.
CheungMC, WolfbauerG, AlbersJJ. Plasma phospholipid mass transfer rate: relationship to plasma phospholipid and cholesteryl ester transfer activities and lipid parameters. Biochim Biophys Acta1303: 103110, 1996.
7.
JiangXC, BruceC, MarJ, LinM, JiY, FranconeOL, TallAR. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J Clin Invest103: 907914, 1999.
8.
TuA-Y, NishidaHI, NishidaT. High-density lipoprotein conversion mediated by human plasma phospholipid transfer protein. J Biol Chem268: 2309823105, 1993.
9.
AlbersJJ, WolfbauerG, CheungMC, DayJR, ChingAFT, LokS, TuA-Y. Functional expression of human and mouse plasma phospholipid transfer protein: effect of recombinant and plasma PLTP on HDL subspecies. Biochim Biophys Acta1258: 2734, 1995.
10.
von EckardsteinA, JauhiainenM, HuangY, MetsoJ, LangerC, PussinenP, WuS, EhnholmC, AssmannG. Phospholipid transfer protein mediated conversion of high density lipoproteins generates prebeta-HDL. Biochim Biophys Acta1301: 255262, 1996.
11.
WolfbauerG, AlbersJJ, OramJF. Phospholipid transfer protein enhances removal of cellular cholesterol and phospholipids by high-density lipoprotein apolipoproteins. Biochim Biophys Acta1439: 6576, 1999.
12.
TuA-Y, AlbersJJ. Glucose regulates the transcription of human genes relevant to HDL metabolism: responsive elements for peroxisome proliferator-activated receptor are involved in the regulation of phospholipid transfer protein. Diabetes50: 18511856, 2001.
13.
UrizarNL, DowhanDH, MooreDD. The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression. J Biol Chem275: 3931339317, 2000.
14.
TuA-Y, AlbersJJ. DNA sequences responsible for reduced promoter activity of human phospholipid transfer protein by fibrate. Biochem Biophys Res Commun264: 802807, 1999.
15.
BoulyM, MassonD, GrossB, JiangX-C, FievetC, CastroG, TallAR, FruchartJ-C, StaelsB, LagrostL, LucG. Induction of the phospholipid transfer protein gene accounts for the high density lipoprotein enlargement in mice treated with fenofibrate. J Biol Chem276: 2584125847, 2001.
16.
MurdochSJ, CarrMC, HokansonJE, BrunzellJD, AlbersJJ. PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance. J Lipid Res41: 237244, 2000.
17.
CheungMC, KnoppRH, RetzlaffB, KennedyH, WolfbauerG, AlbersJJ. Association of plasma phospholipid transfer protein activity with IDL and buoyant LDL: impact of gender and adiposity. Biochim Biophys Acta1587: 5359, 2002.
18.
AlbersJJ, PitmanW, WolfbauerG, CheungMC, KennedyH, TuA-Y, MarcovinaSM, PaigenB. Relationship between phospholipid transfer protein activity and HDL level and size among inbred mouse strains. J Lipid Res40: 295301, 1999.
OramJF. Receptor-mediated transport of cholesterol between cultured cells and high-density lipoproteins. Methods Enzymol129: 645659, 1986.
21.
LowryOH, RosebroughNJ, FarrAL, RandallRJ. Protein measurement with the Folin phenol reagent. J Biol Chem193: 265275, 1951.
22.
MurdochSJ, WolfbauerG, KennedyH, MarcovinaSM, CarrMC, AlbersJJ. Differences in reactivity of antibodies to active versus inactive PLTP significantly impacts PLTP measurement. J Lipid Res43: 281289, 2002.
23.
WittmaackFM, GafvelsME, BronnerM, MatsuoH, McCraeKR, TomaszewskiJE, RobinsonSL, StricklandDK, StraussJFIII. Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport. Endocrinology136: 340348, 1995.
24.
GoldsteinJL, BrunschedeGY, BrownMS. Inhibition of the proteolytic degradation of low density lipoprotein in human fibroblasts by Chloroquine, Concanavalin A, and Triton WR1339. J Biol Chem250: 78547862, 1975.
25.
WarshawskyI, BuG, SchwartzAL. Identification of domains on the 39-kDa protein that inhibit the binding of ligands to the low density lipoprotein receptor-related protein. J Biol Chem268: 2204622054, 1993.
26.
LaDuMJ, ShahJA, ReardonCA, GetzGS, BuG, HuJ, GuoL, Van EldikLJ. Apolipoprotein E receptors mediate the effects of beta-amyloid on astrocyte cultures. J Biol Chem275: 3397433980, 2000.
27.
FavataMF, HoriuchiKY, ManosEJ, DaulerioAJ, StradleyDA, FeeserWS, Van DykDE, PittsWJ, EarRA, HobbsF, CopelandRA, MagoldaRL, ScherlePA, TrzaskosJM. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem273: 1862318632, 1998.
28.
GoueliSA, HsiaoK, LuT, SimpsonD. A novel, selective and potent inhibitor of MAP kinase kinase (MEK). Promega Notes69: 68, 1998.
29.
MetzlerB, LiC, HuY, SturmG, Ghaffari-TabriziN, XuQ. LDL stimulates mitogen-activated protein kinase phosphatase-1 expression, independent of LDL receptors, in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol19: 18621871, 1999.
Scott-BurdenT, ResinkTJ, HahnAW, BaurU, BoxRJ, BuehlerFR. Induction of growth-related metabolism in human vascular smooth muscle cells by low density lipoprotein. J Biol Chem264: 1258212589, 1989.
32.
SunH, CharlesCH, LauLE, TonksNK. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell75: 487493, 1993.
33.
ChuY, SolskiPA, Khosravi-FarR, KellyK. The mitogen-activated protein kinase phosphatases PACI, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. J Biol Chem271: 64976501, 1996.
34.
KusuharaM, ChaitA, CaderA, BerkBC. Oxidized LDL stimulates mitogen-activated protein kinases in smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol17: 141148, 1997.
35.
SachinidisA, SeewaldS, EppingP, SeulC, KoY, VetterH. The growth-promoting effect of low-density lipoprotein may be mediated by a pertussis toxin-sensitive mitogen-activated protein kinase pathway. Mol Pharmacol52: 389397, 1997.
36.
KitaN, MitsushitaJ, OhiraS, TakagiY, AshidaT, KanaiM, NikaidoT, KonishiI. Expression and activation of MAP kinases, ERK1/2, in the human villous trophoblasts. Placenta24: 164172, 2003.
37.
LiC, XuQ. Mechanical stress-initiated signal transductions in vascular smooth muscle cells. Cell Signal12: 435445, 2000.
38.
HunterT. Protein kinases and phosphatases: the Yin and Yang of protein phosphorylation and signaling. Cell80: 225236, 1995.
39.
KnoppRH, WarthMR, CharlesD, ChildsM, LiJR, MabuchiH, and Van AllenMI. Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effect of diabetes. Biol Neonate50: 297317, 1986.
40.
KnoppRH, BonetB, ZhuX-D. Lipid metabolism in pregnancy. In: CowettRM Ed. Principles of Perinatal-Neonatal Metabolism (2nd ed.). New York: Springer, p 221, 1998.
41.
DesoyeG, SchweditschMO, PfeifferKP, ZechnerR, KostnerGM. Correlation of hormones with lipid and lipoprotein levels during pregnancy and postpartum. J Clin Endocrinol Metab64: 704712, 1987.
42.
AlbersJJ, TuAY, PaigenB, ChenH, CheungMC, MarcovinaSM. Transgenic mice expressing human phospholipid transfer protein have increased HDL/non-HDL cholesterol ratio. Int J Clin Lab Res26: 262267, 1996.
43.
JiangX-C, FranconeOL, BruceC, MilneR, MarJ, WalshA, Breslow, TallAR. Increased preβ-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes. J Clin Invest96: 23732380, 1996.
44.
JiangX-C, BruceC, MarJ, LinM, JiY, FranconeOL, TallAR. Targeted mutation of plasma phospholipid transfer protein gene markedly reduced high-density lipoprotein levels. J Clin Invest103: 907914, 1999.
45.
LascuncionMA, BonetB, KnoppRH. Mechanism of the HDL-2 stimulation of progesterone secretion in cultured placental trophoblast. J Lipid Res32: 10731087, 1991.
