Disease relevance of adenosine diphosphate ribose

• Exoenzyme S (ExoS), which has been implicated as a virulence factor of Pseudomonas aeruginosa, catalyzes transfer of the ADP-ribose moiety of NAD+ to many eukaryotic cellular proteins [1].
• Studies of the mechanism of this effect show that a major alteration of poly(ADP-ribose) metabolism caused by hyperthermia involves a decrease in the rate of turnover of polymers of ADP-ribose [2].
• These results suggested that a larger amount of monomers and short oligomers of ADP-ribose was synthesized in adenomatous polyps, while a smaller number of longer polymers was produced in cancers as compared with normal mucosa [3].
• To determine the amino acid that served as the ADP-ribose acceptor, radiolabel from [adenine-U-14C]NAD was incorporated, in the presence of pertussis toxin, into the alpha subunit of transducin (0.3 mol/mol) [4].
• Activation of Ca(2+)-dependent currents in cultured rat dorsal root ganglion neurones by a sperm factor and cyclic ADP-ribose [5].

High impact information on adenosine diphosphate ribose

• The effector, SPN (S. pyogenes NAD-glycohydrolase), is capable of producing the potent second messenger cyclic ADP-ribose, and SLO and SPN act synergistically to trigger cytotoxicity [6].
• DNA binding by PARP triggers primarily its own modification by the sequential addition of ADP-ribose units to form polymers; this modification, in turn, causes the release of PARP from DNA ends [7].
• Inositol 1,4,5-trisphosphate (IP3) is believed to release Ca2+ from the endoplasmic reticulum, but we have now tested whether the Ca(2+)-releasing messengers IP3 and cyclic ADP-ribose (cADPr) can liberate Ca2+ from AGs [8].
• Inositol trisphosphate and cyclic ADP-ribose-mediated release of Ca2+ from single isolated pancreatic zymogen granules [8].
• ATP-dependent accumulation and inositol trisphosphate- or cyclic ADP-ribose-mediated release of Ca2+ from the nuclear envelope [9].

Chemical compound and disease context of adenosine diphosphate ribose

• Using a procedure which allowed the radiolabeling and detection of endogenous polymers of ADP-ribose, we have analyzed the nuclear distribution of these polymers in untreated cells and in cells subjected to hyperthermia, N-methyl-N'-nitro-N-nitrosoguanidine, or both [10].
• Escherichia coli ADP-ribose (ADPR) pyrophosphatase (ADPRase), a Nudix enzyme, catalyzes the Mg(2+)-dependent hydrolysis of ADP-ribose to AMP and ribose 5-phosphate [11].
• The identification of cyclic ADP-ribose as a key signal metabolite in the complex cascade of events triggered by lipopolysaccharide and eventually leading to enhanced generation of pro-inflammatory molecules may suggest a new therapeutic target for treatment of neurodegenerative diseases related to microglia activation [12].
• In the absence of G-proteins but in the presence of NAD and cysteine, pertussis toxin generated a hydroxylamine-sensitive product, suggesting that a free ADP-ribose intermediate, expected to be formed by the NADase activity of the toxin, reacted with cysteine [13].
• Gi, Go, and transducin (ADP-ribosylated by pertussis toxin) and elongation factor II (EF-II) (ADP-ribosylated by pseudomonas exotoxin) all reacted with ADP-ribose antibodies [14].

Biological context of adenosine diphosphate ribose

• Thus, CD38 controls neutrophil chemotaxis to bacterial chemoattractants through its production of cyclic ADP-ribose, and acts as a critical regulator of inflammation and innate immune responses [15].
• This activation can lead to cell death through depletion of beta-nicotinamide adenine dinucleotide (the source of ADP-ribose) and adenosine triphosphate [16].
• It is known that CD38 catalyzes nicotinamide adenine dinucleotide (NAD+) hydrolysis into cyclic ADP-ribose (cADPR) and ADPR [17].
• Discovering new ADP-ribose polymer cycles: protecting the genome and more [18].
• PARP is a nuclear protein that catalyzes the formation of ADP-ribose polymers in response to DNA damage [19].

Anatomical context of adenosine diphosphate ribose

• Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose [20].
• Furthermore, we show that cyclic ADP-ribose can directly induce intracellular Ca++ release in neutrophils and is required for sustained extracellular Ca++ influx in neutrophils that have been stimulated by the bacterial chemoattractant, formyl-methionyl-leucyl-phenylalanine (fMLP) [15].
• Cyclic ADP-ribose (cADPR) is a natural compound that mobilizes calcium ions in several eukaryotic cells [20].
• Cyclic ADP-ribose in insulin secretion from pancreatic beta cells [21].
• Release of Ca2+ from individual plant vacuoles by both InsP3 and cyclic ADP-ribose [22].

Associations of adenosine diphosphate ribose with other chemical compounds

• Poly (ADP-ribose) polymerase is a eukaryotic chromosomal enzyme which utilizes the ADP-ribose moiety of NAD to synthesize the nucleic acid homopolymer (ADP-ribose)n (ref. 1). The precise function of (ADP-ribose)n has not been fully established although it does covalently modify chromosomal proteins by ADP-ribosylation [23].
• All-trans-retinoic acid stimulates synthesis of cyclic ADP-ribose in renal LLC-PK1 cells [24].
• Cholecystokinin potentiates the response to acetylcholine, making it global rather than local, an effect mediated specifically by cyclic ADP-ribose receptors [25].
• Purified GDH was ADP-ribosylated in a cysteine residue in the presence of the mitochondrial activity that transferred the ADP-ribose from NAD+ onto the acceptor site [26].
• Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)-dependent Sir2 histone/protein deacetylases [27].

Gene context of adenosine diphosphate ribose

• ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology [28].
• The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr) [29].
• The hydrolysis of poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase (PARG) was also required, since specific PARG inhibitors, which limit the production of ADP-ribose molecules, restored the function of ABC transporters [30].
• We have recently characterized the protein product of the human NUDT9 gene as a highly specific ADP-ribose (ADPR) pyrophosphatase [31].
• The role of NUDT5 in maintaining levels of free ADP-ribose in cells is discussed [32].

Analytical, diagnostic and therapeutic context of adenosine diphosphate ribose

• Analysis of the reaction product by paper chromatography and Dowex 1 column chromatography indicated that the split product contained the ADP-ribose moiety but was not exactly identical with ADP-ribose [33].
• Based on crystallography of the bacterial toxins, these regions are believed to form, in part, the catalytic site consistent with a common mechanism for the ADP-ribose transfer reaction [34].
• Since this enzyme, which transfers ADP-ribose units to chromatin proteins, is known to activate DNA ligase, we attempted to determine whether ligation of one or both types of DNA break is required for monocytic differentiation [35].
• To investigate this, we used highly purified recombinant ART2 and demonstrated that ART2 catalyzes the formation of an ADP-ribose polymer by sequencing gel and by HPLC and MS/MS mass spectrometry identification of PR-AMP, a breakdown product specific to poly(ADP-ribose) [36].
• The active metabolite was purified by an identical high pressure liquid chromatography (HPLC) procedure used for cyclic ADP-ribose [37].

References