Disease relevance of ribosylhypoxanthine monophosphate

• Mycophenolic acid and virazole are inhibitors of inosinate dehydrogenase and produce growth inhibition and loss of viability in cultured murine lymphoma L5178Y cells [1].
• The mechanism of the cellular toxicity of four inosinate dehydrogenase (IMP-DH) inhibitors with different antitumor and antiviral pharmacological profiles was investigated in mouse lymphoma (S-49) cell culture [2].
• Mycophenolic acid, an inhibitor of inosinate dehydrogenase, had cytostatic and cytotoxic effects on cultured neuroblastoma cells [3].
• Variations in the contribution of induced interferon and adjuvanticity to the antiviral effect of different polyinosinic acid . polycytidylic acid formulations in mice infected with encephalomyocarditis virus [4].
• Adjuvant effects of low doses of a nuclease-resistant derivative of polyinosinic acid . polycytidylic acid on antibody responses of monkeys to inactivated Venezuelan equine encephalomyelitis virus vaccine [5].

High impact information on ribosylhypoxanthine monophosphate

• Furthermore, the degradation of WHHL-VLDL was not blocked by either fucoidin, polyinosinic acid, or polyguanylic acid, potent inhibitors of the acetylated (acetyl)-LDL binding site, or by acetyl-LDL [6].
• Moreover, when mice treated with the urate oxidase inhibitor potassium oxonate were fed inosine or inosinic acid, serum UA levels were elevated markedly for a period of hours, whereas only a minor, transient increase in serum inosine was detected [7].
• Uptake of Aco-HSA liposomes by both endothelial and Kupffer cells was inhibited by preinjection with polyinosinic acid, indicating the involvement of scavenger receptors in the uptake process [8].
• Inhibitors of scavenger receptor binding, including polyinosinic acid and fucoidin, also prevented binding of the oxidized red blood cells [9].
• Rather than inhibiting chemotaxis, acetyl LDL showed intrinsic positive chemotactic activity as did also fucoidin and polyinosinic acid, both of which also interact with the acetyl-LDL receptor [10].

Chemical compound and disease context of ribosylhypoxanthine monophosphate

• Pretreatment of monocytes with scavenger receptor inhibitors, polyinosinic acid (100 microg/ml) and dextran sulfate (50 microg/ml) attenuated CXCR2 expression, but pertussis toxin or cholera toxin had no effect [11].
• Retinoic acid and polyriboinosinic acid act synergistically to enhance the antibody response to tetanus toxoid during vitamin A deficiency: possible involvement of interleukin-2 receptor-beta, signal transducer and activator of transcription-1, and interferon regulatory factor-1 [12].
• With E. coli overproducing the mutated acid phosphatase, 101 g of 5'-IMP per liter (192 mM) was synthesized from inosine in an 88% molar yield [13].
• Our results show that drugs such as 2'3'-dideoxyadenosine (used in HIV therapy) and ribavirin (an inhibitor of inosinate dehydrogenase), in addition to their other known mechanisms of action, have an inhibitory effect on SAH-hydrolase activity, which may be of significance in their antiviral action [14].
• Extensive biochemical alterations including enhanced activity of IMP dehydrogenase, increased inosinate and guanylate pools, and reduced uptake of tiazofurin were found in the hepatoma line resistant to tiazofurin [15].

Biological context of ribosylhypoxanthine monophosphate

• We conclude that Kupffer cells are mainly responsible for the removal of damaged red cells from the blood circulation, a process mediated by polyinosinic acid- and phosphatidylserine-sensitive scavenger receptors, different from scavenger receptor class A type I and II [16].
• However, an enzyme activity that catalyzed the phosphorylation of tiazofurin in the presence of inosine-5'-monophosphate as donor and Mg2+ was detected in the extracts of both wild-type cells and adenosine kinase-deficient mutants [17].
• Increased inosine-5'-phosphate dehydrogenase gene expression in solid tumor tissues and tumor cell lines [18].
• Compounds known to inhibit uptake of LDL via the scavenger receptor, namely, acetylated LDL, polyinosinic acid, dextran sulfate, fucoidan, and polyvinyl sulfate, inhibited both endocytosis of LDL and cell-mediated killing [19].
• Amplification of the inosinate dehydrogenase gene in Trypanosoma brucei gambiense due to an increase in chromosome copy number [20].

Anatomical context of ribosylhypoxanthine monophosphate

• 5'-Nucleotidase, the enzyme which catalyzes the dephosphorylation of 5'-AMP or 5'-IMP to adenosine or inosine, respectively, was found to be located primarily on the external membranes and mitochondria of proximal tubule cells, but not in distal tubule or collecting duct cells [21].
• Polyinosinic acid, a known inhibitor of the scavenger receptor, prevented the uptake by liver endothelial cells [22].
• The scavenger receptor ligand polyinosinic acid inhibited both the cell association and degradation of oxidized LDL in macrophages by greater than 75%, suggesting a common uptake pathway for degraded LDL and nondegraded LDL [23].
• The C3H/HeJ mice have normal numbers of B cells, which are capable of normal responses to other B cell mitogens, such as polyinosinic acid (Poly I) [24].
• Association of 125I-OxLDL could be completely blocked by OxLDL, and partially by acetylated LDL and polyinosinic acid, indicating the presence of a specific binding site for OxLDL on macrophage-derived foam cells [25].

Associations of ribosylhypoxanthine monophosphate with other chemical compounds

• Complexing with polyinosinic acid also decreased the rate of degradation of [35S]MPC as evidenced by an increase of the trichloroacetic acid-precipitable fraction (i.e., oligonucleotides larger than five to ten nucleotide units), from 0.45 to 0.92 of the total radioactivity in plasma 60 min postinjection [26].
• Polyanionic ligands of the macrophage scavenger receptor (SR) for acetylated-LDL caused marked inhibition of AM binding of the oxide particles and latex beads (e.g., TiO2 binding; polyinosinic acid (polyl), 10 micrograms/ml: 70.2 +/- 1.5% inhibition, mean +/- SE, n = 11) [27].
• Linkage of the loci for glucose-6-phosphate dehydrogenase and for inosinic acid pyrophosphorylase to the X chromosome of the field-vole Microtus agrestis [28].
• We now find that, in the presence of MgCl2, KCl, and inosine-5'-monophosphate as phosphate donor, purified cytosolic 5'-nucleotidase catalyzed the phosphorylation of ddlno [29].
• The observed stimulation in macrophage uPA secretion by heparin is similar to that previously reported for polyanions recognized by the scavenger receptor including fucoidan, polyinosinic acid, dextran sulfate, and acetyl-LDL (Falcone and Ferenc: J. Cell. Physiol., 135:387-396, 1988) [30].

Gene context of ribosylhypoxanthine monophosphate

• Polyinosinic acid induces TNF and NO production as well as NF-kappaB and AP-1 transcriptional activation in the monocytemacrophage cell line RAW 264.7 [31].
• Polyinosine: polycytidylic acid (poly I:C), a TLR3 ligand, led to a 9-fold increase [32].
• Polyinosinic acid (poly I) exhibited a concentration-dependent inhibition of the oxLDL-induced effect suggesting that SR II/I but not CD36 interactions are critical to PKC activation [33].
• RLP-stimulated superoxide and tumor necrosis factor-alpha levels were significantly lowered with decreased expression of VCAM-1 and MCP-1 by transfection with As-LOX-1 as did polyinosinic acid (10 microg/ml, a LOX-1 receptor inhibitor) [34].
• Yet, the interaction of these two polyanions with sMARCO is of much lower affinity than that of polyinosinic acid, a polyanionic inhibitor of bacterial binding to MARCO [35].

Analytical, diagnostic and therapeutic context of ribosylhypoxanthine monophosphate

• Circular dichroism calculations for polyinosinic acid in proposed multi-stranded geometries [36].
• To investigate this, we retrospectively analyzed serum samples from nine chronic progressive MS patients who were treated with monthly intravenous infusions of the interferon inducer polyinosinic acid polycytidylic acid polylysine in carboxymethylcellulose (poly ICLC) [37].
• The results of immunoblotting revealed that dextran sulfate (DS), heparin, single-stranded (ss) DNA, and polyinosinic acid (poly I) inhibit interaction between immunoglobulins (Ig) from human autoimmune sera and many polypeptides with various molecular mass [38].
• Inosinic acid 5'-monophosphate dehydrogenase of Escherichia coli: purification by affinity chromatography and some properties [39].
• Fragments of characterised fibres were analysed by HPLC for ATP, inosine-monophosphate (IMP), phosphocreatine (PCr) and creatine levels [40].

References