Temat: nucleotides - Prolib Integro

Skocz do pozycji: 1.

Tytuł:: Increased activity of vascular adenosine deaminase in atherosclerosis and therapeutic potential of its inhibition
Autorzy:: Lango, Romuald
Kutryb-Zajac, Barbara
Toczek, Marta
Jablonska, Patrycja
Slominska, Ewa M.
Sitek, Barbara
Smolenski, Ryszard T.
Rogowski, Jan
Mateuszuk, Łukasz
Chłopicki, Stefan
Zakrzewska, Agnieszka
Zukowska, Paulina
Zabielska, Magdalena A.
Jasztal, Agnieszka
Opis:: Aims Extracellular nucleotides and adenosine that are formed or degraded by membrane-bound ecto-enzymes could affect atherosclerosis by regulating the inflammation and thrombosis. This study aimed to evaluate a relation between ecto-enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the vessel wall with the severity or progression of experimental and clinical atherosclerosis. Furthermore, we tested whether the inhibition of adenosine deaminase will block the development of experimental atherosclerosis. Methods and results Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase 1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-) and wild-type mice as well as in human aortas. Plaques were analysed in the entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein Martius Scarlet Blue staining and vascular accumulation of macrophages. The cellular location of ecto-enzymes was analysed by immunofluorescence. The effect of eADA inhibition on atherosclerosis progression was studied by a 2-month deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already at the age of 1 month and progressed along atherosclerosis development, reaching a 10-fold difference at 10 months. The activity of eADA correlated with atherosclerotic changes in human aortas. High abundance of eADA in atherosclerotic vessels originated from activated endothelial cells and macrophages. There were no changes in ecto-nucleoside triphosphate diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice, suppressed vascular inflammation and improved endothelial function. Conclusions This study highlights the importance of extracellular nucleotides and adenosine metabolism in the atherosclerotic vessel in both experimental and clinical setting. The increased eADA activity marks an early stage of atherosclerosis, contributes to its progression and could represent a novel target for therapy.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 2.

Tytuł:: Chronological lifespan extension and nucleotide salvage inhibition in yeast by isonicotinamide supplementation
Autorzy:: Enriquez-Hesles, Elisa
Wang, Dezhen
Smith, Jeffrey S.
Saha, Shekhar
Letai, Christopher T.
Singh, Pankaj K.
Kalita, Agata
Dinda, Manikarna
Mishra, Swarup
Power, Lindsey N.
Opis:: Isonicotinamide (INAM) is an isomer of the $NAD^{+}$ precursor nicotinamide (NAM) that stimulates the enzymatic activity of Sir2, an $NAD^{+}$-dependent histone deacetylase from the budding yeast, Saccharomyces cerevisiae. Supplementing INAM into growth media promotes the replicative lifespan (RLS) of this single cell organism by maintaining intracellular $NAD^{+}$ homeostasis. INAM also extends yeast chronological lifespan (CLS), but the underlying mechanisms remain largely uncharacterized. To identify cellular pathways potentially impacted by INAM, in this study we perform a chemical genomics screen of the yeast knockout (YKO) collection for mutants sensitized to growth inhibition by INAM. Significant Gene Ontology (GO) terms for candidate genes include transcription elongation factors, metabolic pathways converging on one-carbon metabolism, and de novo purine biosynthesis, collectively suggesting that INAM perturbs nucleotide metabolism. Indeed, INAM causes dose-dependent depletion of intracellular cytidine, uridine, and guanosine, ribonucleosides derived from the breakdown of nucleotide monophosphates (NMPs) via nucleotidases (Phm8, Sdt1, Isn1) or the alkaline phosphatase Pho8. We also find that INAM directly inhibits recombinant nucleotidase activity using cytidine or nicotinamide mononucleotide (NMN) as substrates and inhibits alkaline phosphatase activity quantitated from whole cell extracts. Lastly, we find that Phm8 and Pho8 are specifically required for INAM-induced CLS extension, implicating them as likely functional targets in vivo. Taken together, the findings suggest a model whereby partial impairment of nucleotide and/or $NAD^{+}$ salvage pathways by INAM can trigger a hormetic stress response that supports enhanced quiescence during chronological aging.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 3.

Tytuł:: Hydrolysis of cyclic GMP in rat peritoneal macrophages.
Autorzy:: Witwicka, Hanna
Kobiałka, Marcin
Gorczyca, Wojciech
Tematy:: signal transduction
phosphodiesterases
cyclic nucleotides
macrophages; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1043691.pdf Link otwiera się w nowym oknie
Opis:: Intact rat peritoneal macrophages (rPM) treated with 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases (PDEs), accumulated more cGMP than untreated cells. A PDE activity toward [3H]cGMP was detected in the soluble and particulate fractions of rPM. The hydrolysis of cGMP was Ca2+/calmodulin-independent but increased in the presence of cGMP excess. Similar results were obtained when [3H]cAMP was used as a substrate. The hydrolytic activity towards both nucleotides was inhibited in the presence of IBMX. Therefore, the PDEs of families 2, 5, 10 and 11 are potential candidates for cGMP hydrolysis in the rPM. They may not only regulate the cGMP level in a feedback-controlled way but also link cGMP-dependent pathways with those regulated by cAMP.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 4.

Tytuł:: The effects of galactosamine on UTP levels in the livers of young, adult and old rats.
Autorzy:: Kmieć, Zbigniew
Smoleński, Ryszard
Zych, Marek
Myśliwski, Andrzej
Tematy:: liver
UTP
rat aging
galactosamine
nucleotides; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1044358.pdf Link otwiera się w nowym oknie
Opis:: Galactosamine (GalN), a well-known hepatotoxin that depletes the cellular pool of uracil nucleotides, was previously shown to have greater impact on the inhibition of protein synthesis in hepatocytes of old rats as compared with young animals (Kmieć 1994, Ann. N.Y. Ac. Sci. 717, 216-225). In the present study we compared the effects of GalN on the nucleotide content (measured by ion-exchange HPLC) in the livers of young (4 months), adult (12 months), and old (24-26 months old) rats two hours after its intraperitoneal administration. UTP content of the livers of old control rats was significantly lower (by 28%) than that of young animals. GalN administration decreased the UTP content in the livers of young, adult and old rats by, respectively, 55%, 65% and 89%, and increased the content of UDP-sugars by 189%, 175% and 305%. The hepatic content of ATP, ADP, AMP, NAD, GTP except CTP did not differ significantly among the age groups of rats studied, and was not changed by GalN treatment. The content of CTP was significantly higher in old rats (P < 0.03) upon GalN treatment. The lower hepatic content of UTP may partially explain the increased sensitivity of hepatocytes and livers of old rats to the action of galactosamine, and possibly to other hepatotoxic compounds that decrease transcription in the liver.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 5.

Tytuł:: Degradation of extracellular nucleotides and their analogs in HeLa and HUVEC cell cultures.
Autorzy:: Gendaszewska-Darmach, Edyta
Maszewska, Maria
Zakłos, Małgorzata
Koziołkiewicz, Maria
Tematy:: nucleotide analogs
extracellular nucleotides
ectoenzymes
nucleotide pyrophosphatase; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1043368.pdf Link otwiera się w nowym oknie
Opis:: The use of nucleotides and their analogs in the pharmacological studies of nucleotide receptors (P2 class) should be preceded by detailed studies on their degradation connected with ecto-enzymes of a given cell type. In the present studies we have analyzed stability of some phosphorothioate and phosphonate analogs of ATP and ADP in the HeLa epitheloid carcinoma and endothelial HUVEC cells cultures. Our studies have revealed that ecto-nucleotide pyrophosphatase (E-NPP) is one of the main enzymes involved in the extracellular degradation of ATP and other nucleotides in the HeLa cells. On the other hand, the ecto-ATPDase is responsible for the hydrolysis of extracellular nucleotides in human endothelial cell cultures, while the E-NPP-like enzymes of the HUVEC cells are not essential to this degradation. The concerted action of the aforementioned ecto-enzymes and nucleotide pyrophosphatase, 5'-nucleotidase and adenosine deaminase present in fetal bovine serum (FBS) supplied to the culture medium, results in partial or complete degradation of the phosphorothioate (ATPγS) and phosphonate analogs of adenosine nucleotides (α,β-methylene-ATP and β,γ-methylene-ATP) in the cell cultures. Only ADPβS appears to be resistant to these enzymes. The influence of some nucleotides and their analogs on the proliferation of the HeLa cells in presence or absence of FBS is also discussed.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 6.

Tytuł:: A new approach to phosphorylation of nucleosides using oxyonium phosphobetaines as intermediates
Autorzy:: Materna, Magdalena
Stawinski, Jacek
Sobkowski, Michał
Tematy:: synthesis
phosphorylation
N-oxides
nucleotides
oxyonium phosphobetaines
H-phosphonates; Pokaż więcej
Wydawca:: Polska Akademia Nauk. Czasopisma i Monografie PAN
Powiązania:: https://bibliotekanauki.pl/articles/16673995.pdf Link otwiera się w nowym oknie
Opis:: Oxyonium phosphobetaines are recently discovered molecules with a unique ¯O–P–O–N⁺ bond system, which makes them useful and versatile intermediates for the synthesis of phosphates and their derivatives. In this paper, the preliminary data on the application of these compounds in nucleoside phosphorylation were presented.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 7.

Tytuł:: Particulate guanylyl cyclases: multiple mechanisms of activation.
Autorzy:: Kobiałka, Marcin
Gorczyca, Wojciech
Tematy:: signal transduction
calcium-binding proteins
guanylyl cyclases
cyclic nucleotides; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1044281.pdf Link otwiera się w nowym oknie
Opis:: Cyclic GMP (cGMP), a key messenger in several signal transduction pathways, is synthesized from GTP by a family of enzymes termed guanylyl cyclases, which are found in two forms: cytosolic (soluble) and membrane-bound (particulate). The past decade has brought significant progress in understanding the molecular mechanisms that underlie the regulation of particulate guanylyl cyclases and new members of their family have been identified. It has become more evident that the basic mechanism of catalysis of guanylyl cyclases is analogous to that recognized in adenylyl cyclases. Here we review the known basic mechanisms that contribute to the regulation of particulate guanylyl cyclases.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 8.

Tytuł:: Building the library of RNA 3D nucleotide conformations using the clustering approach
Autorzy:: Zok, T.
Antczak, M.
Riedel, M.
Nebel, D.
Villmann, T.
Lukasiak, P.
Blazewicz, J.
Szachniuk, M.
Tematy:: RNA nucleotides
conformer library
torsion angles
clustering
neural gas; Pokaż więcej
Wydawca:: Uniwersytet Zielonogórski. Oficyna Wydawnicza
Powiązania:: https://bibliotekanauki.pl/articles/329744.pdf Link otwiera się w nowym oknie
Opis:: An increasing number of known RNA 3D structures contributes to the recognition of various RNA families and identification of their features. These tasks are based on an analysis of RNA conformations conducted at different levels of detail. On the other hand, the knowledge of native nucleotide conformations is crucial for structure prediction and understanding of RNA folding. However, this knowledge is stored in structural databases in a rather distributed form. Therefore, only automated methods for sampling the space of RNA structures can reveal plausible conformational representatives useful for further analysis. Here, we present a machine learning-based approach to inspect the dataset of RNA three-dimensional structures and to create a library of nucleotide conformers. A median neural gas algorithm is applied to cluster nucleotide structures upon their trigonometric description. The clustering procedure is two-stage: (i) backbone- and (ii) ribose-driven. We show the resulting library that contains RNA nucleotide representatives over the entire data, and we evaluate its quality by computing normal distribution measures and average RMSD between data points as well as the prototype within each cluster.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 9.

Tytuł:: Determination of adenine nucleotides and their metabolites in human saliva.
Autorzy:: Kochańska, Barbara
Smoleński, Ryszard
Knap, Narcyz
Tematy:: uric acid
xanthine
HPLC
inosine
saliva
hypoxanthine
adenine nucleotides; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1044347.pdf Link otwiera się w nowym oknie
Opis:: The profile and normal concentrations of nucleotide metabolites in human saliva and reproducibility of these determinations were analyzed. Samples of human saliva collected from healthy individuals at weekly intervals, were deproteinized and analysed for the content of adenine nucleotides and their metabolites by reversed-phase HPLC. Initial ATP, hypoxanthine and uric acid concentrations were 0.52 ± 0.15 μM, 1.91 ± 0.37 μM and 184 ± 22 μM respectively. A substantial individual variation persisted within 3 weeks of sampling excepted hypoxanthine which showed some unrelated variations. Determination of nucleotides and their catabolites in saliva due to its simplicity and reproducibility, may be of clinical value in diagnosis of local or systemic disorders.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 10.

Tytuł:: Metabolism of cyclic GMP in peritoneal macrophages of rat and guinea pig.
Autorzy:: Kobiałka, Marcin
Witwicka, Hanna
Siednienko, Jakub
Gorczyca, Wojciech
Tematy:: guinea pig
rat
signal transduction
phosphodiesterases
guanylyl cyclases
protein kinases
cyclic nucleotides
macrophages; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1043463.pdf Link otwiera się w nowym oknie
Opis:: The aim of our studies was to establish which enzymes constitute the "cGMP pathway" in rat and guinea pig peritoneal macrophages (PM). We found that in guinea pig PM synthesis of the nucleotide was significantly enhanced in response to activators of soluble guanylyl cyclase (sGC) and it was only slightly stimulated by specific activators of particulate guanylyl cyclases (pGC). In contrast, rat PM responded strongly to atrial natriuretic peptide (ANP), the activator of pGC type A. The rat cells synthesized about three-fold more cGMP than an equal number of the guinea pig cells. The activity of phosphodiesterases (PDE) hydrolyzing cGMP was apparently regulated by cGMP itself in PM of both species and again it was higher in the rat cells than in those isolated from guinea pig. However, guinea pig PM revealed an activity of Ca2+/calmodulin-dependent PDE1, which was absent in the rat cells. Using Western blotting analysis we were unable to detect the presence of cGMP-dependent protein kinase 1 (PKG1) in PM isolated from either species. In summary, our findings indicate that particulate GC-A is the main active form of GC in the rat PM, while in guinea pig macrophages the sGC activity dominates. Since the profiles of the PDE activities in rat and guinea pig PM are also different, we conclude that the mechanisms regulating cGMP metabolism in PM are species-specific. Moreover, our results suggest that targets for cGMP other than PKG1 should be present in PM of both species.
Dostawca treści:: Biblioteka Nauki

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