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Adv Exp Med Biol. 1997;419:381-8.

Intramolecular ADP-ribose transfer reactions and calcium signalling. Potential role of 2'-phospho-cyclic ADP-ribose in oxidative stress.

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  • 1Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536, USA.


Intramolecular ADP-ribose transfer reactions result in the formation of cyclic ADP-ribose (cADPR) and 2'-phospho-cyclic ADP-ribose (P-cADPR) from NAD and NADP, respectively. The potent Ca2+ releasing activity of these cyclic nucleotides has led to the postulation that they function as second messengers of Ca2+ signalling. The synthesis and hydrolysis of cADPR and P-cADPR are catalyzed by NAD(P) glycohydrolases, but the metabolic signals that regulate their metabolism are poorly understood. To investigate the physiological roles of cADPR and P-cADPR, it is essential to have methods that allow the routine measurement of these nucleotides in cellular systems. As described here, a sensitive and selective radioimmunoassay (RIA) for cADPR has been adapted to search for the natural occurrence of P-cADPR in mammalian tissues. Perchloric acid extracts prepared from bovine tissues and purified by anion exchange chromatography were found to contain immunoreactive material which was identified as P-cADPR. P-cADPR may play an important role in oxidative stress as a link between NADP(H) metabolism and alteration of intracellular Ca2+ homeostasis.

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