Expression of CD38 increases intracellular calcium concentration and reduces doubling time in HeLa and 3T3 cells

Elena Zocchi, Antonio Daga, Cesare Usai, Luisa Franco, Lucrezia Guida, Santina Bruzzone, Aurora Costa, Carla Marchetti, Antonio De Flora

Research output: Contribution to journalArticle

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Abstract

CD38 is a bifunctional ectoenzyme, predominantly expressed on hematopoietic cells during differentiation, that catalyzes the synthesis (cyclase) and the degradation (hydrolase) of cyclic ADP-ribose (cADPR), a powerful calcium mobilizer from intracellular stores. Due to the well established role of calcium levels in the regulation of apoptosis, proliferation, and differentiation, the CD38/cADPR system seems to be a likely candidate involved in the control of these fundamental processes. The ectocellular localization of the cyclase activity, however, contrasts with the intracellular site of action of cADPR. Here we demonstrate that ectocellular expression of human CD38 in CD38- HeLa and 3T3 cells results in intracellular CD38 substrate (NAD+ + NADH) consumption and product (cADPR) accumulation. Furthermore, a causal relationship is established between presence of intracellular cADPR, partial depletion of thapsigargin-sensitive calcium stores, increase in basal free cytoplasmic calcium concentration, and decrease of cell doubling time. The significant shortening of the S phase in CD88+ HeLa cells, as compared with controls, demonstrates an effect of intracellular cADPR on the mammalian cell cycle.

Original languageEnglish
Pages (from-to)8017-8024
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number14
DOIs
Publication statusPublished - Apr 3 1998

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Cyclic ADP-Ribose
3T3 Cells
HeLa Cells
Calcium
NAD
ADP-ribosyl Cyclase
Thapsigargin
S Phase
Cell Differentiation
Cell Cycle
Cells
Apoptosis
Degradation
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Expression of CD38 increases intracellular calcium concentration and reduces doubling time in HeLa and 3T3 cells. / Zocchi, Elena; Daga, Antonio; Usai, Cesare; Franco, Luisa; Guida, Lucrezia; Bruzzone, Santina; Costa, Aurora; Marchetti, Carla; De Flora, Antonio.

In: Journal of Biological Chemistry, Vol. 273, No. 14, 03.04.1998, p. 8017-8024.

Research output: Contribution to journalArticle

Zocchi, E, Daga, A, Usai, C, Franco, L, Guida, L, Bruzzone, S, Costa, A, Marchetti, C & De Flora, A 1998, 'Expression of CD38 increases intracellular calcium concentration and reduces doubling time in HeLa and 3T3 cells', Journal of Biological Chemistry, vol. 273, no. 14, pp. 8017-8024. https://doi.org/10.1074/jbc.273.14.8017
Zocchi, Elena ; Daga, Antonio ; Usai, Cesare ; Franco, Luisa ; Guida, Lucrezia ; Bruzzone, Santina ; Costa, Aurora ; Marchetti, Carla ; De Flora, Antonio. / Expression of CD38 increases intracellular calcium concentration and reduces doubling time in HeLa and 3T3 cells. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 14. pp. 8017-8024.
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AU - Costa, Aurora

AU - Marchetti, Carla

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