Intramolecular ADP-ribose transfer reactions and calcium signalling. Potential role of 2'-phospho-cyclic ADP-ribose in oxidative stress.
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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Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536, USA.
Coyle
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Tai
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Jacobson
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Jacobson
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MK
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction
C098663:cyclic ADP-ribose 2'-phosphate; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009249:NADP; D002118:Calcium