Disease relevance of GPLD1

• Effect of glycosylphosphatidylinositol specific phospholipase D gene expression levels on complement mediated killing of leukemic cells in patients with chronic myeloid leukemia [1].
• Whereas normal keratinocytes did not express significant amounts of GPI-PLD mRNA, expression was dramatically induced by serum in immortalized HaCaT keratinocytes and constitutively high and independent of serum in tumorigenic A431 epidermoid carcinoma cells [2].
• Immunolocalization of a glycosylphosphatidylinositol-specific phospholipase D in mast cells found in normal tissue and neurofibromatosis lesions [3].
• Glycosylphosphatidylinositol-specific phospholipase d in nonalcoholic Fatty liver disease: a preliminary study [4].
• Hypoxia exerted a downregulating effect on this pathway and reoxygenation restored GPLD activation to levels seen during normoxia; however, supraphysiological concentrations of cytokines were able to reverse this pattern [5].

High impact information on GPLD1

• An endogenous glycosylphosphatidylinositol-specific phospholipase D releases basic fibroblast growth factor-heparan sulfate proteoglycan complexes from human bone marrow cultures [6].
• Intact or trypsinized GPI-PLD bound 45Ca2+ (approximately 5.5 ions/molecule GPI-PLD; Kd approximately 16.1 microM as determined by equilibrium dialysis) which could not be blocked by the addition of other divalent metal ions [7].
• The data suggest that the predicted integrin E-F hand-like sites in GPI-PLD are functional but not directly involved in enzymatic activity [7].
• Production of the glycosylphosphatidylinositol-specific phospholipase D by the islets of Langerhans [8].
• Insulin resistance is associated with alterations in proteins involved in lipid metabolism including glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), which is involved in triglyceride metabolism [4].

Biological context of GPLD1

• These data are the first demonstrating that phosphorylation may regulate GPI-PLD interaction with other proteins [9].
• These results suggest that increased serum GPI-PLD is associated with the insulin resistance [10].
• GPI-PLD levels directly correlated with cholesterol, apolipoprotein AI, triglycerides, insulin, and homeostasis model assessment (HOMA) but not C-reactive protein [10].
• Using this contig, we localized 124 sequence tagged sites, expressed sequence tags, and short tandem repeats including most of the markers in linkage with reading disability phenotypes, succinic semialdehyde dehydrogenase, GPLD1, prolactin, and 18 uncharacterized genes [11].
• Southern blot analysis shows that the human genome contains only one GPLD gene and we could only detect one of the two previously reported cDNAs [12].

Anatomical context of GPLD1

• Protein kinase A phosphorylation did not activate GPI-PLD activity in vitro, nor did phosphorylated GPI-PLD cleave a GPI-anchored protein from intact porcine erythrocytes [9].
• Since GPI-PLD is synthesized by, and secreted from, pancreatic islet beta cells, the present study examined the hypothesis that GPI-PLD associates with islet amyloid [13].
• Similarly, in human epithelial cells of the skin, GPI-PLD mRNA expression increased with tumor progression [2].
• This possibility was supported by studies in which exposure of a macrophage cell line to H2O2 led to a 50+/-3% increase in steady-state GPI-PLD mRNA levels [14].
• Glycosylphosphatidylinositol-specific phospholipase D is expressed by macrophages in human atherosclerosis and colocalizes with oxidation epitopes [14].

Associations of GPLD1 with chemical compounds

• GPI-PLD binding to heparan sulphate proteoglycan was determined in the absence or presence of heparan sulphate or heparin [13].
• Further characterization of the GPI-PLD-containing lipoproteins by gel-filtration chromatography and nondenaturing polyacrylamide and agarose gel electrophoresis revealed that these apoA-I-containing particles/complexes were small (8 nm) and migrated with pre-beta particles on agarose electrophoresis [15].
• To determine the distribution of GPI-PLD among lipoproteins and characterize the GPI-PLD-containing lipoproteins in human plasma, we used dextran sulfate and immunoaffinity chromatography to isolate apolipoprotein-specific lipoproteins [16].
• Down-regulation of glycosylphosphatidylinositol-specific phospholipase D induced by lipopolysaccharide and oxidative stress in the murine monocyte- macrophage cell line RAW 264.7 [17].
• The half-life of GPI-PLD mRNA was not affected by LPS, or decreased slightly with H(2)O(2), indicating that the reduction in GPI-PLD mRNA is due primarily to transcriptional regulation [17].

Other interactions of GPLD1

• However, we found that hCAP18 and GPI-PLD, along with apoA-I, are common components of both lytic and non-lytic primate HDLs [18].
• Phosphorylation also inhibits binding of GPI-PLD to apolipoprotein AI [9].
• Heparan sulphate proteoglycan, which is commonly present in most amyloid, bound GPI-PLD in vitro [13].
• Fibril formation from human islet amyloid polypeptide was determined in the absence or presence of GPI-PLD [13].
• Expression of GPI-PLD mRNA by human macrophages was confirmed in vitro by reverse transcription/polymerase chain reaction [14].

Analytical, diagnostic and therapeutic context of GPLD1

• Immunoprecipitation of GPI-PLD with a monoclonal antibody to GPI-PLD co-precipitated apoA-I and apoA-IV but little or no apoA-II, apoC-II, apoC-III, apoD, or apoE [15].
• We have therefore developed a semi-quantitative RT-PCR method to measure mRNA expression of all known GPI-PLD isoforms in cells and tissues [2].
• Further characterization of the GPI-PLD-containing lipoproteins by gel filtration chromatography, nondenaturing poly-acrylamide and agarose gel electrophoresis revealed that GPI-PLD was restricted to an apolipoprotein AI-containing particle or complex that was small (apparent mean Mw of 140 kDa) and distinct from the bulk of HDL [16].
• METHODS AND RESULTS: Immunohistochemistry using human GPI-PLD-specific rabbit polyclonal antiserum was performed on a total of 83 nonatherosclerotic and atherosclerotic human coronary arteries from 23 patients [14].
• In cases of systemic inflammatory response syndrome, sepsis, and septic shock, the activity of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in serum amounts to 20 to 25% of the activity found in a healthy control group [19].

References