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

• Analysis of covariance also demonstrated that the use of alcohol was associated with higher HDL cholesterol (P < 0.04), whereas plasma LCAT, CETP and PLTP activity levels were not related to alcohol consumption [6].

High impact information on PLTP

• The cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) are members of the lipid transfer/lipopolysaccharide binding gene family [7].
• Edman degradation of MTPv1 isolated from transfected cells revealed three unique residues; however, recombinant MTP and MTPv1 had an equivalent protein disulfide isomerase association, subcellular localization, triglyceride transfer, phospholipid transfer, response to inhibitors, and ability to support apoB secretion [8].
• Enhancement of phospholipid transfer from Sendai virus to erythrocytes is mediated by target cell membrane [9].
• In addition, the present study demonstrated that the PLTP-mediated net mass transfer of alpha-tocopherol can constitute a new mechanism for the incorporation of alpha-tocopherol into the vascular wall in addition to the previously recognized LDL receptor and lipoprotein lipase pathways [10].
• The facilitated transfer reaction of alpha-tocopherol could be blocked by specific anti-PLTP antibodies [10].

Chemical compound and disease context of PLTP

• Decreases in plasma EST and CET in such patients, as well as a low PLTP activity in acromegaly suggest that reverse cholesterol transport may be impaired, contributing to increased cardiovascular risk [11].
• Fenofibrate stimulated liver fatty acid beta-oxidation, increased the transcriptional expression of carnitine palmitoyltransferase 1 and phospholipid transfer protein, and decreased expression of apoA-I and apoC-III [12].

Biological context of PLTP

• It is proposed that plasma PLTP mass levels are related to glucose metabolism rather than to lipid metabolism [3].
• Bezafibrate-induced diminished insulin resistance is associated with a reduction of CET and PLTP activity [13].
• Weak associations were also observed between PLTP parameters and determinants of glucose homeostasis (glucose, insulin, and homeostasis model assessment for insulin resistance) [14].
• The decrease in plasma PLTP activity after insulin was larger in B1B1 than in B2B2 homozygotes (P < 0.05) [15].
• The present data on PLTP activity and concentration reveal novel connections of the two PLTP forms to lipid and carbohydrate metabolism [14].

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

• CETP activity was influenced by race and PLTP by age [20].
• Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro [5].
• ApoA-IV proteoliposomes also activated LA-PLTP in a concentration-dependent manner, whereas apoA-I proteoliposomes had no such effect [21].

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

• Mean plasma phospholipid transfer protein (PLTP) concentrations were measured for the first time by using a competitive enzyme-linked immunosorbent assay [3].
• Size-exclusion chromatography of tear fluid indicated that PLTP eluted in a position corresponding to a size of 160-170 kDa [23].
• Anti-apoE immunoaffinity chromatography and Western blot analyses indicated that some CSF PLTP is associated with apoE-containing lipoproteins [5].
• PLTP activity was positively related to body mass index (P < 0.01), waist to hip circumference ratio (P < 0.001), as well as to fasting blood glucose (P < 0.05) and plasma C-peptide (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)[24]
• METHODS: Low-density lipoprotein (LDL) subfractions were measured by density gradient ultracentrifugation and plasma PLTP and CETP activities by radiometric assays in 240 diabetic patients and 136 controls [25].

References