ADP-ribose

Endonuclease-catalyzed hydrolysis of DNA at the internucleosomal linker regions into multimers of 180 base pairs which are visualized by electrophoresis as a ladder of nuclear DNA fragments. Access of the endonuclease to DNA is facilitated by depletion of polyamines, and the activity of the enzyme is mcrea.sed by and decreased by ADP-tibosylation. Thus, agents that increase intracellular Ca " or inhibit l>oly(ADP-ribose) polymerase can induce apoptosi.s. ... 

Researchers found that NAD serves as a substrate in poly(ADP-ribose) synthesis, a reaction important for DNA repair processes. In addition, it takes part in mono (ADP-ribosyl)ation reactions that are involved in endogenous regulation of many aspects of signal transduction and membrane trafficking in eukaryotic cells. 

Pertussis toxin is produced by the bacterium Bordetella pertussis. It covalently modifies G-proteins of the G/Go family (transfer of a ADP-ribose moiety of NAD onto G-protein a-subunits). ADP-ribosylated G-proteins are arrested in their inactive state and, as a consequence, functionally uncoupled from their respective effectors. Examples for pertussis toxin-sensitive cellular responses include the hormonal inhibition of adenylyl cyclases, stimulation ofK+ channels, inhibition of Ca2+ channels and stimulation ofthe cGMP-phosphodiesterase in retinal rods. 

In addition to its coenzyme role, NAD is the source of ADP-ribose for the ADP-ribosylation of proteins and polyADP-ribosylation of nucleoproteins involved in the DNA repair mechanism. 

Poly(ADP-ribose)polyrmerase (PARP) inhibitors, 42 (2004) 125 P2 Purinoreceptor ligands, 38 (2001) 115 p38 MAP kinase inhibitors, 38 (2001) 1 Paclitaxel, anticancer agent, 32 (1995) 289... 

Ame J-C et al. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem 1999 274 17860-17868. 

The knockout of PARP-1 or PARP-2 significantly reduces the cells ability to repair damaged DNA following their exposure to radiation or cytotoxic insult [6,7]. Poly (ADP-ribose) polymer synthesis consumes substantial amounts of NAD+, and hyperactivation of PARP results in depletion of cellular NAD+ pools and energy stores, leading to cell death by necrosis. 

It is known that peroxynitrite is able to induce DNA strand breakage, which activates nuclear enzyme poly(ADP ribose) synthase (PARS). Szabo et al. [257] showed that the inhibition of PARS by oral treatment with lipophilic inhibitor 5-iodo-6-amino-l,2-benzopyr-one delayed the onset of arthritis in rats. It is possible that infrared pulse laser therapy can be useful for the treatment of RA patients [258]. 

G proteins can be modified by ADP-ribosylation catalyzed by certain bacterial toxins. Among the tools that facilitated the discovery and characterization of G proteins were the bacterial toxins cholera and pertussis, which were known to influence adenylyl cyclase activity. Subsequently, it was shown that the actions of these toxins are achieved by their ability to catalyze the addition of an ADP-ribose group donated from nicotinamide adenine dinucleotide (NAD) to specific amino acid residues in certain heterotrimeric G protein a subunits [ 1 ]. 

Ataxia telangiectasia mutated (ATM), poly(ADP ribose) polymerase (PARP), DNA-dependent protein kinase, DNA replication factor C, DNA topoisomerase I, DNA fragmentation factor (DFF)45, inhibitor of caspase-activated DNAse (ICAD), lamins A, Bl, and C TRAF-1, Rafl, Ras, GAP, GDP dissociation inhibitor of Rho family GTPases, phospholipase A2, Statl... 

NAD+ is a substrate for pertussis toxin, allowing the transfer of an ADP-ribose derivatives to G-proteins. Ruoho used [125I]-iodoazidophenylpropionyl-NAD+... 

The aryl azido derivatives of [32P]NAD+ were employed to site-specifically incorporate photoactivatable ADP-riboses to transducin at Cys-347 by means of pertussis toxin, and the conjugation was followed by irradiation. Photocrosslinking revealed three major bands after irradiation which corresponded to a-y(47 kDa), a-a (83 kDa),and a-a-a (105kDa) subunit contact domains [88]. 

Messmer, U.K. et al., Nitric oxide induced poly(ADP-ribose) polymerase cleavage in RAW264.7 macrophage apoptosis is blocked by Bcl-2, FEES Lett., 384, 162, 1996. 

Perraud A-L, Fleig A, Dunn CA 2001 ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411 595—599 Sanders KM 2001 Mechanisms of calcium handling in smooth muscles. J Appl Physiol 91 1438-1449... 

Eisner For a spark, most of it isn t lost, but from a wave which will see the surface membrane, you will lose a lot. This then comes back to the question of cyclic ADP ribose, FK506 and so on that may potentiate Ca2+ release from the SR, but in the presence of these things you will end up with less Ca2+ in the SR. 

Wilson HL, Dipp M, Thomas JM, Lad C, Galione A, Evans AM 2001 ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase act as a redox sensor. A primary role for cyclic ADP-ribose in hypoxic pulmonary vasoconstriction. J Biol Chem 276 11180-11188... 

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