Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP

S. Takasawa, A. Tohgo, N. Noguchi, T. Koguma, K. Nata, T. Sugimoto, H. Yonekura, H. Okamoto

Research output: Contribution to journalArticlepeer-review

250 Citations (Scopus)

Abstract

Cyclic ADP-ribose (cADPR) has been recently shown to be generated in pancreatic β-cells by glucose stimulation, serving as a second messenger for Ca2+ mobilization in the endoplasmic reticulum in the process of insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In the present study, we isolated a cDNA for CD38, which has been reported to be a human leukocyte antigen, from a human insulinoma and expressed the cDNA in COS-7 cells. CD38 expression was observed in the plasma membrane and the microsome fractions of the COS-7 cells. When we incubated the plasma membrane fraction with NAD+ and analyzed the reaction products by high pressure liquid chromatography, the formation of cADPR was observed in addition to the ADP-ribose (ADPR) formation. When the plasma membrane fraction was incubated with cADPR, cADPR was converted to ADPR stoichiometrically. These results suggest that CD38 has both cADPR- forming and -hydrolyzing activities. Moreover, we found that ATP (2-10 mM), generated in the glucose metabolism in β-cells, inhibited the cADPR- hydrolyzing activity, resulting in the increased formation of cADPR. These findings indicate a role for CD38 in the synthesis and hydrolysis of cADPR in the process of insulin secretion in pancreatic β-cells.

Original languageEnglish
Pages (from-to)26052-26054
Number of pages3
JournalJournal of Biological Chemistry
Volume268
Issue number35
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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