Disease relevance of PCYT1A

• Vibrio cholerae non-O1 strains were screened for the presence of cholera enterotoxin (CT) genes by means of digoxigenin-labelled polynucleotide CTA and CTB probes [1].
• The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97-3.67) [2].
• We report here that the pretreatment with CT 105 for 24 h at a 10 microM concentration increases intracellular calcium concentration by about twofold in SK-N-SH and PC 12 cells, but not in U251 cells, originated from human glioblastoma [3].
• The results of this study showed that CT 105 disrupts calcium homeostasis and renders neuronal cells more vulnerable to glutamate-induced excitotoxicity, and that some portion of CT 105 has partial beta-sheet conformation in various environments, which may be related to the self-aggregation and toxicity [3].
• Neuropsychological studies in patients who have suffered traumatic brain injury show that the eventual clinical outcome is frequently worse than might be predicted from using conventional (CT or T(1)/T(2)-weighted MRI) imaging [4].

High impact information on PCYT1A

• Furthermore, these results suggest that regulation of alternative processing of CT/CGRP could occur at the level of polyadenylation, rather than splicing [5].
• Two similar antigens, mouse cytochrome c (mcyt c) and pigeon cytochrome c (pcyt c), elicit T cell responses in strains of mice bearing MHC class II Ek beta Ek alpha (B10.A), Eb beta Ek alpha [B10.A(5R)], and Es beta Ek alpha [B10.S(9R)] [6].
• The decrease in INSCAT expression in late passages of cells serially cultured in 11.1 mM glucose was associated with the inability to form a specific nuclear protein-DNA complex with the CT motifs of the human insulin promoter [7].
• In this article, we present direct absorption measurements of the long-range CT over a 140-A DNA assembly based on a GC repetitive sequence constructed by simply mixing DNA building blocks [8].
• We show that a CT through DNA nanoscale assembly is possible and programmable with the designed DNA sequence [8].

Chemical compound and disease context of PCYT1A

• CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population [2].
• In addition, the calcium increase and toxicity induced by CT 105 were reduced by cholesterol and MK 801 in SK-N-SH and PC 12 cells, whereas the toxicity of Abeta(1-42) was attenuated by nifedipine and verapamil [3].
• Colocalisation of CTP:choline phosphate cytidylyltransferase (CT) with F-actin accompanies increased phosphatidylcholine synthesis in differentiating neuroblastoma cells [9].
• We studied 16 adults with chronic bronchial asthma by measuring the plasma theophylline concentrations and evaluating clinically the control of asthma following oral administration of choline theophyllinate (CT) and a sustained-release theophylline preparation (SRT) [10].
• The present study was conducted to compare the diagnostic accuracy between carbon-11 choline (11C-choline) positron emission tomography (PET)/computed tomography (CT) and conventional imaging for the staging of bone and soft tissue sarcomas [11].

Biological context of PCYT1A

• Here we report that FOH-induced apoptosis in CHO cells caused a dose-dependent activation of CCT alpha and inhibition of the final step in the pathway, resulting in a biphasic effect on PtdCho synthesis [12].
• Nuclear export of CCT alpha appeared to be an active process in FOH-treated CHO cells that was independent of caspase removal of the nuclear localization signal [12].
• To investigate the role of this region in PC biosynthesis, A549 and L2 cells were transfected with cDNA for CT mutants under the control of a glucocorticoid-inducible long terminal repeat (LTR) promoter [13].
• The region which deviates most from the rat liver CT sequence is near the C-terminus, where 7 changes are clustered within 34 residues (345-359), of the putative phosphorylation domain [14].
• Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109 [2].

Anatomical context of PCYT1A

• Activation of CCT alpha was accompanied by enzyme translocation to the nuclear envelope within 30 min of FOH addition to cells [12].
• CTP:phosphocholine cytidylyltransferase alpha (CCT alpha) is a nuclear enzyme that catalyzes the rate-limiting step in the CDP-choline pathway, the primary route for synthesis of phosphatidylcholine (PtdCho) in eukaryotic cells [12].
• These results suggest that the CT region located between residues 267 and 277 from the N-terminus is required for the interaction of CT with membranes [13].
• The membrane-binding characteristics of the CT fusion proteins were also examined using intact lung microsomes [13].
• The specific activity of the HCT in COS cell homogenates was the same as that of analogously expressed rat liver CT [14].

Associations of PCYT1A with chemical compounds

• CT-B binds to ganglioside GM1, which functions as the plasma membrane receptor for CT, and the enzymatic activity of A1 causes the toxic effects of CT on target cells [15].
• Activation of CT A by treatment with dithiothreitol (20 mM) also does not affect detergent binding [16].
• The weak hydrophobic nature of CT A is also reflected by the negative modulatory action of anionic phospholipids and deoxycholate on its mono-ADP-ribosyltransferase activity and the ability of the former to decrease its intrinsic fluorescence intensity in a salt-resistant way [16].
• The addition of oleate to cytosol followed by incubation at 37 degrees C resulted in the formation of aggregates containing both CT and CTBP [17].
• The aggregates eluted in the void volume of the gel filtration column, sedimented to the bottom of glycerol density gradients, and precipitated at concentrations of polyethylene glycol lower than required to precipitate CT and CTBP in untreated cytosol [17].

Physical interactions of PCYT1A

• CT consists of one A polypeptide and five B polypeptides associated by noncovalent bonds, and CT-B interacts with CT-A primarily via the A2 domain [15].

Other interactions of PCYT1A

• Both CT B subunits and to a lesser extent CT A subunits were delivered intact to the serosal surface of the basolateral membrane [18].
• METHODS: This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida [2].

Analytical, diagnostic and therapeutic context of PCYT1A

• Site-directed mutagenesis and in vivo and in vitro expression studies mapped a caspase 6 and/or 8 cleavage site to TEED(28 downward arrow)G, the final residue in the CCT alpha nuclear localization signal [12].
• CT production by the probe-positive strains was confirmed by the immunoassays [1].
• In-vitro production of CT was investigated by the Y1 mouse adrenal cell assay, enzyme-linked immunosorbent assay (ELISA) and a commercial, reversed passive latex agglutination (RPLA) kit [1].
• Human CTP:phosphocholine cytidylyltransferase (CT) cDNAs were isolated by PCR amplification of a human erythroleukemic K562 cell library [14].
• Gel filtration chromatography separated CTBP from CT in liver cytosol [17].

References