Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Choline Deficiency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,657 records · Page 92Linked to original sources
PubMed2004

Genomic hypomethylation is specific for preneoplastic liver in folate/methyl deficient rats and does not occur in non-target tissues.

Chronic dietary insufficiency of the lipotropic nutrients choline and methionine is hepatocarcinogenic in male rats and certain mouse strains. Despite the fact that DNA hypomethylation is a hallmark of most cancer genomes, the tissue-specific consequences of this alternation with respect to tumorigenesis remain to be determined. In the present study, the folate/methyl deficient model of multistage hepatocarcinogenesis was used to evaluate in vivo alterations in DNA methylation in the liver, the carcinogenesis target tissue, and in non-target tissues, including pancreas, spleen, kidney, and thymus, of male F344 rats. By utilizing the HpaII/MspI-based cytosine extension assay, we demonstrated that the percent of CpG sites that lost methyl groups on both strands progressively increased in liver tissue after 9, 18, and 36 weeks of folate/methyl deficiency. The endogenous activity of DNA methyltransferase in liver of rats fed with folate/methyl deficient diet for the 36-week period gradually increased with time. In contrast, non-target tissues displayed no changes in DNA methylation level or activity of DNA methyltransferase. The failure of DNA methyltransferase to restore and maintain DNA methylation patterns in preneoplastic liver tissue may lead to the establishment of tumor-specific DNA methylation and DNA methyltransferase profiles that are not expressed in normal liver. These results provide additional information about alterations in DNA methylation during early preneoplastic stages of carcinogenesis. They also demonstrate that DNA hypomethylation is localized to tissue that undergoes carcinogenesis, and is not altered in non-target tissues.

Animals↗
PubMed2000

BDNF is needed for postnatal maturation of basal forebrain and neostriatum cholinergic neurons in vivo.

Neurotrophins regulate survival, neurite outgrowth, and phenotypic maturation of developing neurons. Brain-derived neurotrophic factor (BDNF) can promote the survival of developing cholinergic forebrain neurons in vitro and reduce their degeneration following injury in adult rats. We investigated the role of endogenous BDNF during postnatal development of these cholinergic neurons by analyzing homozygous BDNF-deficient (-/-) mice and their littermates (+/+, +/-). At P6, the number of choline acetyltransferase- (ChAT) positive neurons in the medial septum was approximately 23% lower in BDNF-/- mice, although their brain and body weight was normal. At P15, control (+/+) littermates had approximately 45% more and approximately 45% larger ChAT-positive neurons and a much denser cholinergic hippocampal innervation than at P6, indicative of maturation of the septohippocampal system. In BDNF-/- mice, the number, size, and ChAT-immunostaining intensity of the cholinergic neurons remained the same between P6 and P15 (few mice survive longer). BDNF-/- mice had about three times more TUNEL-labeled (a marker of apoptosis) cells in the medial septum at P6, consistent with (but not proof of) the possibility that the cholinergic neurons were dying. The cholinergic hippocampal innervation in BDNF-/- mice expanded to a lesser extent than in controls and had reduced levels of acetylcholinesterase staining at P15. The developmental deficits were largely similar in the neostriatum of BDNF-/- mice. These findings suggest that BDNF is critical for postnatal development and maturation of cholinergic forebrain neurons.

Acetylcholine↗
PubMed1992

The effect of lowered extracellular Na+ concentration on ultraviolet light-induced relaxation of vasoconstricted rabbit isolated thoracic aorta.

The effect of lowering extracellular ion concentration on ultraviolet (UV) light-induced photorelaxation of norepinephrine(NE)-constricted rabbit isolated thoracic aorta was investigated. The magnitude of the photorelaxation response (similar to acetylcholine-induced, but not nitroprusside-induced, relaxation) progressively declined, in the absence of an effect on NE-induced vasoconstriction, as the total extracellular ion concentration was progressively reduced. This diminution in the photorelaxation response was duplicated by isosmotic lowering of the extracellular concentration of Na+, but not other ions, from 145 to 25 mM and was not restored by the replenishment of the Na+ deficiency by equimolar amounts of mannitol or Li+. In contrast, choline fully substituted for Na+. These findings suggest a fundamental difference in the ion dependency (and, hence, the mechanisms) of UV-induced photorelaxation and the vasorelaxations induced by acetylcholine or sodium nitroprusside.

Acetylcholine↗
PubMed1998

One-methyl group metabolism in non-ketotic hyperglycinaemia: mildly elevated cerebrospinal fluid homocysteine levels.

Non-ketotic hyperglycinaemia (NKH) is a rare, severe brain disease caused by deficient glycine cleavage enzyme complex activity resulting in elevated glycine concentrations. Recent experience suggests that factors in addition to glycine kinetics are involved in its pathogenesis. The glycine cleavage reaction through the formation of methylenetetrahydrofolate is an important one-methyl group donor. A deficiency in one-methyl group metabolites, in particular of choline, has been hypothesized in NKH. We investigated metabolites involved in one-methyl group metabolism in plasma and CSF of 8 patients with NKH, and monitored the effect of treatment with choline in one patient. Plasma and CSF choline and phosphatidylcholine concentrations were normal, except for a low plasma choline in the single neonate studied. Choline treatment did not change brain choline content, and was not associated with clinical or radiological improvement. Methionine concentrations and, in one-patient, S-adenosylmethionine and 5-methyltetrahydrofolate concentrations were normal in CSF. Homocysteine concentrations in CSF, however, were slightly but consistently elevated in all four patients examined, but cysteine, cysteinylglycine and glutathione were normal. Serine is important in the transfer of one-methyl groups from mitochondria to cytosol. Serine concentrations were normal in plasma and CSF, but dropped to below normal in CSF in three patients on benzoate treatment. These observations add to our understanding of the complex metabolic disturbances in NKH.

Amino Acid Metabolism, Inborn Errors↗
PubMed2001

Two-component system that regulates methanol and formaldehyde oxidation in Paracoccus denitrificans.

A chromosomal region encoding a two-component regulatory system, FlhRS, has been isolated from Paracoccus denitrificans. FlhRS-deficient mutants were unable to grow on methanol, methylamine, or choline as the carbon and energy source. Expression of the gene encoding glutathione-dependent formaldehyde dehydrogenase (fhlA) was undetectable in the mutant, and expression of the S-formylglutathione hydrolase gene (fghA) was reduced in the mutant background. In addition, methanol dehydrogenase was immunologically undetectable in cell extracts of FhlRS mutants. These results indicate that the FlhRS sensor-regulator pair is involved in the regulation of formaldehyde, methanol, and methylamine oxidation. The effect that the FlhRS proteins exert on the regulation of C(1) metabolism might be essential to maintain the internal concentration of formaldehyde below toxic levels.

Aldehyde Oxidoreductases↗
PubMed2002

De novo methylation of the p16INK4A gene in early preneoplastic liver and tumors induced by folate/methyl deficiency in rats.

Previous studies have established that chronic dietary insufficiency of the lipotropic nutrients choline and methionine with or without chemical initiation is hepatocarcinogenic in the rat and certain mouse strains. In the present study, the folate/methyl-deficient model of multistage hepatocarcinogenesis was used to evaluate progressive in vivo changes in p16 promoter methylation in both preneoplastic and tumor tissues. Previous studies using this model have demonstrated stage-dependent alterations in genome-wide and p53 gene-specific methylation. In the present study, we used highly sensitive methylation specific PCR (MSP) to determine time of appearance of methylated sequences within p16 promoter. In addition, methylation-sensitive single nucleotide primer extension methodology was applied to determine methylation status of the remaining CpG sites within amplified methylated alleles. Using this approach, extensive methylation in p16 promoter was found in 100% of tumors, but the pattern of methylation varied depending on tumor type. The incidence and extent of de novo methylation in the CpG island of the p16 promoter increased with tumor progression. To further explore the evolution of p16 gene hypermethylation, we examined the appearance and progression of site-specific de novo methylation during early preneoplasia. Our data show that site-specific de novo methylation of 5' CpG island of p16 gene precedes tumor development and undergoes dynamic expansion during tumor progression.

Adenoma↗
PubMed1977

A methionine-reversible folate deficiency in rats following the acute administration of diethylnitrosamine and alpha-naphthylisothiocyanate.

Acute doses of the hepatotoxic agents diethylnitrosamine (DEN) and alpha-naphthylisothiocyanate (ANIT) to young adult male rats led to the production of a folate deficiency as determined by an elevated urinary excretion of formiminoglutamic acid (FIGLU) 2 to 4 days following administration of the compounds. High dietary levels of methionine significantly reduced the elevated levels of FIGLU produced by the 2 chemicals. Dietary folate had no significant effect on the excretion of urinary FIGLU. Although the hepatic levels of S-adenosylmethionine (SAM) were significantly increased in rats fed the high dietary levels of methionine, an acute dose of DEN did not depress the hepatic levels of SAM. The results indicate that the methyl-reversible folate deficiency caused by hepatotoxic agents is not the direct consequence of altered hepatic levels of SAM.

1-Naphthylisothiocyanate↗
PubMed1992

Osmoprotectants and phosphate regulate expression of phospholipase C in Pseudomonas aeruginosa.

Phospholipase C has been increasingly recognized as a significant virulence determinant in the pathogenesis of Gram-negative and Gram-positive infections. Pseudomonas aeruginosa carries two, non-tandem genes encoding phospholipase C (PLC) activity. One PLC (PLC-H) haemolyses human and sheep erythrocytes while the other is not haemolytic for these kinds of red blood cells. It was previously determined that the synthesis of both PLCs is regulated by inorganic phosphate (Pi), but little else was known regarding the regulation of these potentially important virulence determinants of P. aeruginosa. In this report, data are presented demonstrating that both PLC genes are regulated at the transcriptional level by Pi and by a P. aeruginosa homologue of the positive regulator of genes in the Pi regulon of Escherichia coli, i.e. PhoB. In addition to Pi, it is also shown in this report that the synthesis of both PLC-H and PLC-N is induced by compounds which are not only derived from the substrate product of both enzymes, i.e. phosphorylcholine, but are also known osmoprotectants in eukaryotic and prokaryotic cells. The osmoprotective derivatives of phosphorylcholine which induce the synthesis of PLC in P. aeruginosa include choline, glycine betaine, and dimethylglycine, but not sarcosine (monomethylglycine) or glycine. By constructing mutants which are deficient in the production of each separate PLC and in the production of PhoB it was determined that induction of PLC-H by the osmoprotective compounds is independent of Pi concentration and PhoB, while induction of PLC-N by these compounds requires Pi-deficient conditions and PhoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1999

CCSP deficiency does not alter surfactant homeostasis during adenoviral infection.

Clara cell secretory protein (CCSP) deficiency in mice is associated with increased susceptibility to pulmonary inflammation after hyperoxia or viral infection. Because adenoviral exposure perturbs pulmonary surfactant homeostasis in vivo, we hypothesized that CCSP deficiency would influence surfactant metabolism after pulmonary infection. Alveolar and total lung saturated phosphatidylcholine pool sizes were similar in CCSP-deficient [CCSP(-/-)] and wild-type [CCSP(+/+)] mice before and 7 days after intratracheal administration of adenovirus. Radiolabeled choline and palmitate incorporation into saturated phosphatidylcholine was similar, and there was no alteration by previous infection 7 days before the incorporation measurements. Furthermore, CCSP deficiency did not influence clearance of [(14)C]dipalmitoylphosphatidylcholine and (125)I-labeled recombinant surfactant protein C. Increased persistence of alveolar capillary leak was observed in CCSP(-/-) mice after adenoviral infection. Surfactant lipid homeostasis was not influenced by CCSP before or after administration of adenovirus to the lung. Persistence of alveolar capillary leak in CCSP(-/-) mice after adenovirus provides further evidence for the role of CCSP in the regulation of pulmonary inflammation.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1984

CDP-choline does not inhibit erythrocyte glycolytic or pentose phosphate pathway enzyme activity.

An increased concentration of cytidine diphosphocholine (CDP-choline) has been observed in erythrocytes in the hemolytic anemia due to hereditary pyrimidine 5'-nucleotidase deficiency (P5Nase, EC 3.1.3.5) and in a patient with a chronic hemolytic anemia not due to P5Nase deficiency, as reported by Paglia and co-workers in 1983. In the current studies, we were unable to demosntrate a significant inhibitory effect of 4 mmol/l CDP-choline on the activities of the enzymes of the Embden-Meyerhof and pentose phosphate pathways. The physiologic significance of increased erythrocytic CDP-choline remains to be determined.

Choline↗
PubMed1966

Inositol deficiency resulting in death: an explanation of its occurrence in Neurospora crassa.

The incorporation of radio-active inositol and choline into the cytoplasmzic membranes of inositol-and choline-auxotrophic mnutants of Neuros-pora crassa revealed that the membrane of particles which contain proteases is relatively poor in lecithin and rich in inositol-phospholipid. In mycelia of the mutant requiring inositol, grown in a suboptimum amount of exogenous inositol, the strlctural initegrity of the protease particles is lost, and the bulk of intracellular protease activity is recovered in the soluble fraction of the cell. Death from this kind of inositol deficiency is interpreted as autolysis of the cytoplasm cautsed by free proteases.

Carbon Isotopes↗
PubMed2003

The lipidation by hepatocytes of human apolipoprotein A-I occurs by both ABCA1-dependent and -independent pathways.

The pathways of hepatic intra- and peri-cellular lipidation of apolipoprotein A-I (apoA-I) were studied by infecting primary mouse hepatocytes from either apoA-I-deficient or ABCA1-deficient mice with a recombinant adenovirus expressing the human apoA-I (hapoA-I) cDNA (endo apoA-I) or incubating the hepatocytes with exogenously added hapoA-I (exo apoA-I) and examining the hapoA-I-containing lipoproteins formed. The cells, maintained in serum-free medium, were labeled with [(3)H]choline, and the cell medium was separated by fast protein liquid chromatography or immunoprecipitated to quantify labeled choline phospholipids specifically associated with hapoA-I. With the apoA-I-deficient hepatocytes, the high density lipoprotein fraction formed with endo apoA-I contained proportionally more phospholipids than that formed with exo apoA-I. However, the lipoprotein size and electrophoretic mobility and phospholipid profiles were similar for exo apoA-I and endo apoA-I. Taken together, these data demonstrate that a significant proportion of hapoA-I is secreted from hepatocytes in a phospholipidated state but that hapoA-I is also phospholipidated peri-cellularly. With primary hepatocytes from ABCA1-deficient mice, the expression and net secretion of adenoviral-generated endogenous apoA-I was unchanged compared with control mice, but (3)H-phospholipids associated with endo apoA-I and exo apoA-I decreased by 63 and 25%, respectively. The lipoprotein size and electrophoretic migration and their phospholipid profiles remained unchanged. In conclusion, we demonstrated that intracellular and peri-cellular lipidation of apoA-I represent distinct and additive pathways that may be regulated independently. Hepatocyte expression of ABCA1 is central to the lipidation of newly synthesized apoA-I but also contributes to the lipidation of exogenous apoA-I. However, a significant basal level of phospholipidation occurs in the absence of ABCA1.

ATP Binding Cassette Transporter 1↗