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Gene Review

PLTP  -  phospholipid transfer protein

Homo sapiens

Synonyms: BPIFE, HDLCQ9, Lipid transfer protein II, Phospholipid transfer protein
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Disease relevance of PLTP

  • Clinical data have recently indicated that plasma PLTP activity and mass were both higher in diabetic patients concomitant with hyperglycemia [1].
  • We examined the effects of 24-h hyperinsulinemia (30 mU x kg(-1) x h(-1)) and 24-h Acipimox (250 mg/4 h) on plasma lipids as well as CETP and PLTP activities (measured with exogenous substrate assays) in eight healthy and eight type 2 diabetic subjects [2].
  • Among non-insulin-dependent diabetes mellitus patients, PLTP levels were positively correlated with fasting glycemia and glycohemoglobin levels (r=0.341, P=0.0220; and r=0.382, P=0.0097, respectively) but not with plasma lipid parameters [3].
  • In contrast, neither CETP mRNA nor CETP activity were detectable in rabbit brain.A role of PLTP in the central nervous system could involve some of its actions previously established in vitro, like proteolysis of apolipoproteins, and be physiologically relevant for neurodegenerative disorders such as Alzheimer's disease [4].
  • We assessed PLTP activity and apoE concentration in CSF of patients with probable AD (n = 50), multiple sclerosis (MS; n = 9), other neurologic diseases (n = 21), and neurologically healthy controls (n = 40) [5].

Psychiatry related information on PLTP


High impact information on PLTP


Chemical compound and disease context of PLTP


Biological context of PLTP


Anatomical context of PLTP

  • The glucose-responsive elements are located between -759 and -230 of the PLTP 5'-flanking region, within which two binding motifs (-537 to -524 and -339 to -327) for either peroxisome proliferator-activated receptor or farnesoid X-activated receptor are involved in this glucose-mediated transcriptional regulation [1].
  • PLTP was able to bind and neutralize LPS: incubation of LPS with purified recombinant PLTP (rPLTP) resulted in the inhibition of the ability of LPS to stimulate adhesive responses of neutrophils, and addition of rPLTP to blood inhibited cytokine production in response to LPS [16].
  • Consistent with these findings, PLTP activity in cerebrospinal fluid amounted to 23% +/- 3% of that in rabbit plasma [4].
  • In situ hybridization studies revealed specific, high-level synthesis of PLTP mRNA in choroid plexus and ependyma, the organs responsible for production of cerebrospinal fluid [4].
  • Exogenous addition of recombinant PLTP to primary human astrocytes significantly increased apoE secretion to the conditioned medium [5].

Associations of PLTP with chemical compounds

  • This finding suggests that high glucose upregulates the transcription of human PLTP gene via nuclear hormone receptors [1].
  • To assess the role of this hydrophobic cluster for the functional activity of PLTP, single point alanine mutants were engineered [17].
  • Plasma PLTP activity was highly, positively, and selectively correlated with the cholesterol concentration of the buoyant LDL/dense IDL fractions, yet demonstrated a complete absence of an association with the dense LDL fractions [18].
  • Only total Lp(A-I) triglyceride in women (not men) (r = 0.71, P = 0.009) was significantly correlated with PLTP activity [19].
  • Bezafibrate-induced change in PLTP activity correlated with change in FFAs (r = 0.455, P = 0.058) [13].

Regulatory relationships of PLTP


Other interactions of PLTP

  • In healthy subjects, the PLTP responses with insulin and Acipimox were larger than the changes in CETP activity (P < 0.05) [2].
  • Multiple sequence alignment suggested that, in PLTP, a cluster of hydrophobic residues substitutes for a cluster of positively charged residues found on the surface of LBP and BPI, which is critical for interaction with lipopolysaccharides [17].
  • In the present study, we used the crystallographic data available for BPI to build a three-dimensional model for PLTP [17].
  • We asked whether PLTP could interact with LPS and mediate the transfer of LPS to lipoproteins or to CD14 [16].
  • Subsequently, phospholipid transfer activities of purified lipid transfer proteins, deprived of LCAT activity, were compared and potential interactions between the two proteins were studied [22].

Analytical, diagnostic and therapeutic context of PLTP


  1. 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. Tu, A.Y., Albers, J.J. Diabetes (2001) [Pubmed]
  2. Plasma phospholipid transfer protein activity is lowered by 24-h insulin and acipimox administration: blunted response to insulin in type 2 diabetic patients. Riemens, S.C., van Tol, A., Sluiter, W.J., Dullaart, R.P. Diabetes (1999) [Pubmed]
  3. Mass concentration of plasma phospholipid transfer protein in normolipidemic, type IIa hyperlipidemic, type IIb hyperlipidemic, and non-insulin-dependent diabetic subjects as measured by a specific ELISA. Desrumaux, C., Athias, A., Bessède, G., Vergès, B., Farnier, M., Perségol, L., Gambert, P., Lagrost, L. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  4. Molecular characterization of rabbit phospholipid transfer protein: choroid plexus and ependyma synthesize high levels of phospholipid transfer protein. Gander, R., Eller, P., Kaser, S., Theurl, I., Walter, D., Sauper, T., Ritsch, A., Patsch, J.R., Föger, B. J. Lipid Res. (2002) [Pubmed]
  5. Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro. Vuletic, S., Peskind, E.R., Marcovina, S.M., Quinn, J.F., Cheung, M.C., Kennedy, H., Kaye, J.A., Jin, L.W., Albers, J.J. J. Neurosci. Res. (2005) [Pubmed]
  6. Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin:cholesterol acyltransferase and lipid transfer protein activity levels. Riemens, S.C., van Tol, A., Hoogenberg, K., van Gent, T., Scheek, L.M., Sluiter, W.J., Dullaart, R.P. Clin. Chim. Acta (1997) [Pubmed]
  7. Plasma lipid transfer proteins. Tall, A. Annu. Rev. Biochem. (1995) [Pubmed]
  8. MTP regulated by an alternate promoter is essential for NKT cell development. Dougan, S.K., Rava, P., Hussain, M.M., Blumberg, R.S. J. Exp. Med. (2007) [Pubmed]
  9. Enhancement of phospholipid transfer from Sendai virus to erythrocytes is mediated by target cell membrane. Kuroda, K., Maeda, T., Ohnishi, S. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  10. Plasma phospholipid transfer protein prevents vascular endothelium dysfunction by delivering alpha-tocopherol to endothelial cells. Desrumaux, C., Deckert, V., Athias, A., Masson, D., Lizard, G., Palleau, V., Gambert, P., Lagrost, L. FASEB J. (1999) [Pubmed]
  11. Low plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins. Beentjes, J.A., van Tol, A., Sluiter, W.J., Dullaart, R.P. Atherosclerosis (2000) [Pubmed]
  12. Paradoxical exacerbation of combined hyperlipidemia in human apolipoprotein A-II transgenic mice treated with fenofibrate. Ribas, V., Palomer, X., Roglans, N., Rotllan, N., Fievet, C., Tailleux, A., Julve, J., Laguna, J.C., Blanco-Vaca, F., Escolà-Gil, J.C. Biochim. Biophys. Acta (2005) [Pubmed]
  13. Decreased PLTP mass but elevated PLTP activity linked to insulin resistance in HTG: effects of bezafibrate therapy. Jonkers, I.J., Smelt, A.H., Hattori, H., Scheek, L.M., van Gent, T., de Man, F.H., van der Laarse, A., van Tol, A. J. Lipid Res. (2003) [Pubmed]
  14. Active and low-active forms of serum phospholipid transfer protein in a normal Finnish population sample. Jänis, M.T., Siggins, S., Tahvanainen, E., Vikstedt, R., Silander, K., Metso, J., Aromaa, A., Taskinen, M.R., Olkkonen, V.M., Jauhiainen, M., Ehnholm, C. J. Lipid Res. (2004) [Pubmed]
  15. Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men. Riemens, S.C., Van Tol, A., Stulp, B.K., Dullaart, R.P. J. Lipid Res. (1999) [Pubmed]
  16. Neutralization and transfer of lipopolysaccharide by phospholipid transfer protein. Hailman, E., Albers, J.J., Wolfbauer, G., Tu, A.Y., Wright, S.D. J. Biol. Chem. (1996) [Pubmed]
  17. A hydrophobic cluster at the surface of the human plasma phospholipid transfer protein is critical for activity on high density lipoproteins. Desrumaux, C., Labeur, C., Verhee, A., Tavernier, J., Vandekerckhove, J., Rosseneu, M., Peelman, F. J. Biol. Chem. (2001) [Pubmed]
  18. Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution. Murdoch, S.J., Carr, M.C., Kennedy, H., Brunzell, J.D., Albers, J.J. J. Lipid Res. (2002) [Pubmed]
  19. Lipoprotein lipase and hepatic lipase: their relationship with HDL subspecies Lp(A-I) and Lp(A-I,A-II). Cheung, M.C., Sibley, S.D., Palmer, J.P., Oram, J.F., Brunzell, J.D. J. Lipid Res. (2003) [Pubmed]
  20. Moderate hyperalphalipoproteinaemia in a Brazilian population is related to lipoprotein lipase activity, apolipoprotein A-I concentration, age and body mass index. Alarcon, S.B., Oliveira, H.C., Harada, L.M., Nunes, V.S., Kaplan, D., Quintão, E.C., de Faria, E.C. Clin. Sci. (2004) [Pubmed]
  21. Apolipoprotein E activates the low-activity form of human phospholipid transfer protein. Jänis, M.T., Metso, J., Lankinen, H., Strandin, T., Olkkonen, V.M., Rye, K.A., Jauhiainen, M., Ehnholm, C. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  22. Comparative study of phospholipid transfer activities mediated by cholesteryl ester transfer protein and phospholipid transfer protein. Lagrost, L., Athias, A., Gambert, P., Lallemant, C. J. Lipid Res. (1994) [Pubmed]
  23. Phospholipid transfer protein is present in human tear fluid. Jauhiainen, M., Setälä, N.L., Ehnholm, C., Metso, J., Tervo, T.M., Eriksson, O., Holopainen, J.M. Biochemistry (2005) [Pubmed]
  24. Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism. Dullaart, R.P., Sluiter, W.J., Dikkeschei, L.D., Hoogenberg, K., Van Tol, A. Eur. J. Clin. Invest. (1994) [Pubmed]
  25. Plasma phospholipid transfer protein activity and small, dense LDL in type 2 diabetes mellitus. Tan, K.C., Shiu, S.W., Wong, Y. Eur. J. Clin. Invest. (2003) [Pubmed]
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