Disease relevance of Pltp

• BLp secretion was diminished in hepatocytes from ApoB-transgenic PLTP-deficient mice, a defect that was corrected when PLTP was reintroduced in adenovirus [1].
• To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice deficient in the gene encoding PLTP (PLTP-deficient mice) using different hyperlipidemic mouse strains [1].
• Thus, the vitamin E transfer activity of PLTP appears to be a key process in preventing oxidative damage in the brain, and PLTP-deficient mice could be a new model of the contribution of oxidative brain injury in the etiology of neurodegenerative diseases [2].
• Phospholipid-transfer activities in cytosols from lung, isolated alveolar type II cells and alveolar type II cell-derived adenomas [3].
• To determine the effect of phospholipid-transfer protein and exogenous phospholipids on the turnover and subcellular distribution of endogenous phospholipids, neuroblastoma cells were preincubated for 48 h in the presence of [methyl-3H]choline and washed [4].

Psychiatry related information on Pltp

• Activity of this transfer protein in cerebrospinal fluid of patients with Alzheimer's disease is profoundly decreased and exogenous phospholipid transfer protein induces apolipoprotein E secretion by primary human astrocytes in vitro [5].

High impact information on Pltp

• In ApoB-transgenic and ApoE-deficient backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and markedly decreased atherosclerosis [1].
• Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency [1].
• 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 [6].
• On a chow diet, PLTP-/- mice showed marked decreases in HDL phospholipid (60%), cholesterol (65%), and apo AI (85%), but no significant change in non-HDL lipid or apo B levels, compared with wild-type littermates [7].
• It has been proposed that the plasma phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids and cholesterol from triglyceride-rich lipoproteins (TRL) into high-density lipoproteins (HDL) [7].

Chemical compound and disease context of Pltp

• Phospholipid transfer protein-mediated incorporation and subcellular distribution of exogenous phosphatidylcholine and sphingomyelin in cultured neuroblastoma cells [8].

Biological context of Pltp

• Sex differences in atherosclerosis in mice with elevated phospholipid transfer protein activity are related to decreased plasma high density lipoproteins and not to increased production of triglycerides [9].
• To evaluate the in vivo role of PLTP in lipoprotein metabolism, we used homologous recombination in embryonic stem cells and produced mice with no PLTP gene expression [7].
• There is down-regulation of the transcripts for phospholipid transfer protein, but up-regulation of those for hepatic lipase and lipoprotein lipase [10].
• The predicted amino acid sequence of mouse phospholipid transfer protein shows the protein to be 476 amino acids long and to have a sequence identity of 83% with that of human phospholipid transfer protein [11].
• The data show that PLTP regulates the bioavailability of vitamin E in atherogenic lipoproteins and suggest a novel strategy for achieving more effective concentrations of anti-oxidants in lipoproteins, independent of dietary supplementation [12].

Anatomical context of Pltp

• The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions [13].
• In mouse peritoneal macrophage cells, PLTP expression was also up-regulated by the LXR/RXR (retinoid X receptor) heterodimer [14].
• This decrease in activity was associated with a similar decrease in phospholipid transfer protein mRNA in lung, adipose tissue, and liver [11].
• We reported here the identification and characterization of phospholipids transfer protein (PLTP), which is highly expressed in the embryo-containing oviduct and localized at the oviductal epithelium by in situ hybridization [15].
• PLTP deficiency tended to reduce sperm motility as shown by a 24% reduction in spermatozoa with progressive motility (P<0.02), with no change in other sperm parameters as compared with wild-type males [16].

Associations of Pltp with chemical compounds

• The HDL was found to be protein-rich (primarily apoA-I) and specifically depleted in phosphatidylcholine (PC) (28% in wild-type mice (WT) vs. 15% in Pltp KO mice, P < 0.001) [17].
• Although in PLTP-deficient mice, the induction of HDL cholesterol as well as HDL particle size increase persisted, the extent of the induction was greatly attenuated [14].
• The plasma phospholipid transfer protein (PLTP) is known to mediate transfer of phospholipids from triglyceride-rich lipoproteins to high density lipoprotein (HDL) and plays a critical role in HDL metabolism [14].
• Overall, we conclude that PLTP deficiency decreases liver vitamin E content, increases hepatic oxidant tone, and substantially enhances ROS-dependent destruction of newly synthesized apoB via a post-ER process [18].
• To determine whether PLTP regulates lipoprotein vitamin E content in vivo, we measured alpha-tocopherol content and oxidation parameters of lipoproteins from PLTP-deficient mice in wild type, apoE-deficient, low density lipoprotein (LDL) receptor-deficient, or apoB/cholesteryl ester transfer protein transgenic backgrounds [12].

Other interactions of Pltp

• Nuclear run-on assay indicated that the effect of LXR agonist on PLTP expression was at the transcriptional level [14].
• HL and PLTP activities did not differ from those in the control group during the whole experimental period [19].
• Altered hepatic lipid status and apolipoprotein A-I metabolism in mice lacking phospholipid transfer protein [20].
• Taken together, our data suggested that PLTP may play important role(s) during in vivo preimplantation embryo development [15].
• Atherosclerosis susceptibility is decreased in mice with PLTP deficiency that is associated with decreased liver production of apoB-containing lipoproteins and increase in their antioxidant [21].

Analytical, diagnostic and therapeutic context of Pltp

• Affymetrix microarray data and Northern blot assays demonstrated that phospholipid transfer protein (PLTP) was induced 6-fold when either murine or human macrophages were incubated in the presence of ligands for the liver X receptor (LXR) and the retinoid X receptor [22].
• More importantly, PLTP mRNA increases in the oviductal epithelia of pregnant, but not pseudo-pregnant mice when assayed by real-time PCR [15].
• These findings suggest that PLTP activity can modulate the effects of an atherogenic diet on high-density lipoproteins [23].
• Finally, immunohistochemistry studies reveal that PLTP is highly expressed by macrophages within human atherosclerotic lesions, suggesting a potential role for this enzyme in lipid-loaded macrophages [13].
• OBJECTIVE: Using bone marrow transplantation, we assessed the impact of macrophage-derived phospholipid transfer protein (PLTP) on lesion development in hypercholesterolemic mice that expressed either normal levels of mouse apolipoprotein AI (apoAI) or elevated levels of only human apoAI [24].

References