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Effect of chlorpromazine on the synthesis, hydrolysis, and transfer of microsomal cytidine liponucleotides and mitochondrial polyglycerophosphatides.

The effect of chlorpromazine on subcellular biosynthesis, hydrolysis, and transfer of lipids and liponucleotides participating in the biosynthesis of polyglycerophosphatides in guinea pig liver was studied. Chlorpromazine showed an apparent stimulation of accumulation of phosphatidic acid and CDP-diglycerides in microsomal membranes and phosphatidylglycerolphosphate in mitochondrial membranes in a concentration-dependent manner that was influenced by incubation time and the nature of fatty acids in CDP-diglycerides. Transfer of membrane-bound CDP-diglycerides from microsomal to mitochondrial m

Для поглощения CTP хламидией трахоматисом требуется преобразование цитидина в CTP в зависимость от UCK2.

Хламидия трахоматис, обязуемая внутриклеточная бактерия, превращается в вакулярное отделение, называемое включением. бактерии импортируют нуклеосайд трифосфаты (НТФ), присутствующие в люмене для включения. Остается неясным, попадают ли нуклеозиды в люмен в их родной форме или в качестве фосфорилатированных нуклеотидов. Используя химию щелчка в сочетании с микроскопией флуоресцентной активности, мы представляем доказательства того, что цитидин требует фосфорилирования с помощью уридина-цитидиновой киназы 2 (UKK2) до его включения в бактериальные нуклеиновые кислоты. Эти выводы подтверждают гипо

Совпадение в аннотации оригинала
Chlamydia trachomatis , an obligate intracellular bacterium, develops into a vacuolar compartment called the inclusion. The bacteria import … ed nucleotides. Using click chemistry coupled with fluorescence microscopy we provide evidence that cytidine requires phosphorylation by host uridine-cytidine kinase 2 (UCK2) prior to its incorporation into bacterial nucleic acids. These findings support the hypothesis that nucleosides are converted into nucleotides in the host cytoplasm prior to transloca …

Deciphering the role of Enterococcus faecium cytidine deaminase in gemcitabine resistance of gallbladder cancer.

Gemcitabine-based chemotherapy is a cornerstone of standard care for gallbladder cancer (GBC) treatment. Still, drug resistance remains a significant challenge, influenced by factors such as tumor-associated microbiota impacting drug concentrations within tumors. Enterococcus faecium, a member of tumor-associated microbiota, was notably enriched in the GBC patient cluster. In this study, we investigated the biochemical characteristics, catalytic activity, and kinetics of the cytidine deaminase of E. faecium (EfCDA). EfCDA showed the ability to convert gemcitabine to its metabolite 2',2'-difluo…

Cytidine deaminase status as a marker of response to azacytidine treatment in MDS and AML patients.

Azacitidine (Aza) is a mainstay of treatment for patients with acute myeloid leukaemia (AML) ineligible for induction chemotherapy and other high-risk myelodysplastic syndromes (MDS). Only half of patients respond, and almost all will eventually relapse. There are no predictive markers of response to Aza. Aza is detoxified in the liver by cytidine deaminase (CDA). Here, we investigated the association between CDA phenotype, toxicity and efficacy of Aza in real-world adult patients. Median overall survival (OS) was 15 months and 13 months in AML and high-risk MDS patients respectively. In addit…

Characterization of Ig gene somatic hypermutation in the absence of activation-induced cytidine deaminase.

Somatic hypermutation (SHM) of Ig genes depends upon the deamination of C nucleotides in WRCY (W = A/T, R = A/G, Y = C/T) motifs by activation-induced cytidine deaminase (AICDA). Despite this, a large number of mutations occur in WA motifs that can be accounted for by the activity of polymerase eta (POL eta). To determine whether there are AICDA-independent mutations and to characterize the relationship between AICDA- and POL eta-mediated mutations, 1470 H chain and 1313 kappa- and lambda-chain rearrangements from three AICDA(-/-) patients were analyzed. The Ig mutation frequency of all V(H) g…

Antitumor activity of cytidine dialdehyde and its effects on nucleotide and nucleic acid synthesis.

Cytidine dialdehyde inhibited the growth of leukemia L1210 cells in culture at a 50% inhibitory concentration of 3.5 X 10(-5) M and, when administered i.p. at 200 mg/kg daily for 5 days, increased the mean survival of L1210 tumor-bearing mice by up to 171%. Given by the s.c. or i.v. routes, the compound was ineffective. The ethanol adduct of cytidine dialdehyde, although inactive in cell culture, increased the mean survival of L1210 tumor-bearing mice by up to 225% when administered i.p. but was inactive upon s.c. administration. Exposure of L1210 cells in culture for 25 hr to cytidine dialdeh…

Activation-induced cytidine deaminase in B cells of hepatits C virus-related cryoglobulinaemic vasculitis.

Immunoglobulin variable region heavy chain (IgVH ) somatic gene diversification is instrumental in the transformation process that characterizes hepatitis C virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to which activation-induced cytidine deaminase (AID), an enzyme essential for IgV gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV) remains unclear. AID mRNA expression in the peripheral blood of 102 chronically hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26 healthy subjects was investigated using real-…

Cytidine diphosphate choline improves the outcome of cardiac arrest vs epinephrine in rat model.

OBJECTIVES: Cytidine diphosphate choline (CDP-choline) is a cholinergic agent that can both stimulate the cholinergic pathway and increase blood pressure. We aimed to investigate the effects of CDP-choline on the outcome of cardiac arrest in comparison with epinephrine. METHODS: This was a randomized prospective animal study. Cardiac arrest was induced by asphyxia in 45 rats. After 7 minutes of asphyxia, resuscitation was attempted. The rats were allocated to different groups treated with 2 mL/kg saline, 100 μg/kg epinephrine, or 250 mg/kg CDP-choline. The hemodynamic parameters were monitore…

A role for host activation-induced cytidine deaminase in innate immune defense against KSHV.

Activation-induced cytidine deaminase (AID) is specifically induced in germinal center B cells to carry out somatic hypermutation and class-switch recombination, two processes responsible for antibody diversification. Because of its mutagenic potential, AID expression and activity are tightly regulated to minimize unwanted DNA damage. Surprisingly, AID expression has been observed ectopically during pathogenic infections. However, the function of AID outside of the germinal centers remains largely uncharacterized. In this study, we demonstrate that infection of human primary naïve B cells with…

(E)-5-[2-(methoxycarbonyl)ethenyl]cytidine as a chemical actinometer for germicidal UV radiation.

(E)-5-[2-(Methoxycarbonyl)ethenyl]cytidine (S) was examined for use as a chemical actinometer for germicidal UV radiation. Its photoproduct, 3-beta-D-ribofuranosyl-2,7-dioxopyrido[2,3-d]pyrimidine (P), is strongly fluorescent with excitation and emission maxima at 330 and 385 nm, respectively. Experiments were conducted to characterize the dynamic behavior of aqueous solutions of S and P when subjected to UV radiation. UV sources used for these experiments included a low-pressure mercury lamp, a XeBr excimer lamp, and a KrCI excimer lamp; all three sources were mounted in collimating devices t…

Activation-induced cytidine deaminase: a dual role in class-switch recombination and somatic hypermutation.

Maturation of the antibody repertoire is mediated by two different mechanisms: class-switch recombination (CSR) and somatic hypermutation (SHM). These two processes are T cell dependent and occur in the germinal centers of secondary lymphoid organs. CSR leads to the production of antibodies of different isotypes whereas SHM leads to the selection of B cells expressing a BCR with high affinity for antigen. The activation-induced cytidine deaminase (AID) was recently shown to play a key role in these two mechanisms, demonstrating for the first time that these maturation processes share a common …

Activation-induced cytidine deaminase promotes DNA demethylation and expression of the Ninjurin-2 gene.

Activation-induced cytidine deaminase (AID) is expressed in germinal center B cells and contributes to somatic hypermutation and isotype switching of immunoglobulins. AID is also reportedly expressed in colonic epithelial cells (CECs) during inflammation. However, the physiological roles of AID in CECs are largely unknown. Here, we identify 619 genes, the expression of which is induced in a colorectal cancer (CRC) cell line (DLD-1) by overexpression of AID. These genes include those associated with the phosphoinositide-3-kinase-protein kinase B, mammalian target of rapamycin and mitogen-activa…

Increased IGF-1 and DNA Synthesis in Patients With Activation-Induced Cytidine Deaminase Deficiency.

OBJECTIVE: To characterize patients with activation-induced cytidine deaminase (AICDA) deficiency, a rare autosomal recessive inborn error of immunity (IEI), and examine the role of insulin-like growth factor-1 (IGF-1) and cellular oxidative stress in the pathogenesis. METHODS: Patients data was retrieved from the Kuwait National Primary Immunodeficiency Registry. Plasma IGF-1 levels were tested by ELISA assay, while bromodeoxyuridine (BrdU) incorporation in peripheral blood mononuclear cells (PBMCs) was used as an index of DNA synthesis. IGF-1 receptor (IGF-1R) protein was measured by immuno…

Non-viral in vivo cytidine base editing in hepatocytes using focused ultrasound targeted microbubbles.

CRISPR-Cas9-based genome editing technologies, such as base editing, have the potential for clinical translation, but delivering nucleic acids into target cells in vivo is a major obstacle. Viral vectors are widely used but come with safety concerns, while current non-viral methods are limited by low transfection efficiency. Here we describe a new method to deliver CRISPR-Cas9 base editing vectors to the mouse liver using focused ultrasound targeted microbubble destruction (FUTMD). We demonstrate, using the example of cytosine base editing of the Pde3b gene, that FUTMD-mediated delivery of cyt

Therapeutic Exon Skipping Through a CRISPR-Guided Cytidine Deaminase Rescues Dystrophic Cardiomyopathy in Vivo.

BACKGROUND: Loss of dystrophin protein causes Duchenne muscular dystrophy (DMD), characterized by progressive degeneration of cardiac and sk … and skeletal muscle defects in these mice. Using this model, we examined the feasibility of using a cytidine base editor to install exon skipping and rescue dystrophic cardiomyopathy in vivo. AAV9-based CRISPR/Cas9-AID (eTAM) together with AAV9-sgRNA was injected into neonatal DmdE4* mice, which were analyzed 2 or 12 months after treatment to evaluate the …

Epstein-Barr Virus Induced Cytidine Metabolism Roles in Transformed B-Cell Growth and Survival.

Epstein-Barr virus (EBV) is associated with 200,000 cancers annually, including B-cell lymphomas in immunosuppressed hosts. Hypomorphic mutations of the de novo pyrimidine synthesis pathway enzyme cytidine 5' triphosphate synthase 1 (CTPS1) suppress cell-mediated immunity, resulting in fulminant EBV infection and EBV+ central nervous system (CNS) lymphomas. Since CTP is a critical precursor for DNA, RNA, and phospholipid synthesis, this observation raises the question of whether the isozyme CTPS2 or cytidine salvage pathways help meet CTP demand in EBV-infected B cells. Here, we found that EBV…