Abstract
We report the kinetics and molecular properties of CD38 purified from bovine lung microsomal membranes after its solubilization with Triton X-100. The enzyme was found to be a novel member of a multicatalytic NAD+-glycohydrolase (NADase, EC 3.2.2.6). It was able to utilize NAD+ in different ways, producing nicotinamide (Nam) and either adenosine diphosphoribose (ADPR, NADase activity) or cyclic ADPR (cADPR, cyclase activity); it also catalyzed the hydrolysis of cADPR to ADPR (cADPR, hydrolase activity). In addition, the enzyme catalyzed the pyridine base exchange reaction with conversion of NAD+ into NAD analogues. These data are evidence that CD38 is involved in the regulation of both NAD+ and calcium-mobilizing agents, the concentration resulting in an essential enzyme that plays a key role in cellular energy and signal-transduction systems.
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Aksoy P, Escande C, White TA, Thompson M, Soares S, Benech JC, Chini EN (2006a) Regulation of SIRT 1 mediated NAD dependent deacetylation: a novel role for the multifunctional enzyme CD38. Biochem Biophys Res Commun 349:353–359
Aksoy P, White TA, Thompson M, Chini EN (2006b) Regulation of intracellular levels of NAD: a novel role for CD38. Biochem Biophys Res Commun 345:1386–1392
Berger F, Ramirez-Hernandez MH, Ziegler M (2004) The new life of a centenarian: signaling functions of NAD(P). Trends Biochem Sci 29:111–118
Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Burkle A (2005) Poly(ADP-ribose). The most elaborate metabolite of NAD+. FEBS J 272:4576–4589
Deshpande DA, White TA, Dogan S, Walseth TF, Panettieri RA, Kannan MS (2005) CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 288:L773–L788
Dousa TP, Chini EN, Beers KW (1996) Adenine nucleotide diphosphates: emerging second messengers acting via intracellular Ca2+ release. Am J Physiol Cell Physiol 271:C1007–C1024
Gale EA (2003) Intervening before the onset of type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT). Diabetologia 46:339–346
Kaanders JH, Bussink J, van der Kogel AJ (2002) A novel biology-based approach in radiotherapy. Lancet Oncol 3:728–737
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Lee HC (2002) Cyclic ADP-ribose and NAADP—structure, metabolism and function. Kluwer, Boston
Lee HC, Munshi C, Graeff R (1999) Structures and activities of cyclic ADP-ribose, NAADP and their metabolic enzymes. Mol Cell Biochem 193:89–98
Magni G, Amici A, Emanuelli M, Orsomando G, Raffaelli N, Ruggieri S (2004) Enzymology of NAD+ homeostasis in man. Cell Mol Life Sci 61:19–34
Orsomando G, Polzonetti V, Natalini P (2000) NAD(P)+-glycohydrolase from human spleen: a multicatalytic enzyme. Comp Biochem Physiol B Biochem Mol Biol 126:89–98
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. J Biol Chem 276:11180–11188
Zhang AY, Li PL (2006) Vascular physiology of a Ca2+ mobilizing second messenger—cyclic ADP-ribose. J Cell Mol Med 10:407–422
Ziegler M (2000) New functions of a long-known molecule. Emerging roles of NAD in cellular signalling. Eur J Biochem 267:1550–1564
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Polzonetti, V., Pucciarelli, S., Vita, A. et al. CD38 in Bovine Lung: A Multicatalytic NADase. J Membrane Biol 227, 105–110 (2009). https://doi.org/10.1007/s00232-008-9149-x
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DOI: https://doi.org/10.1007/s00232-008-9149-x