Regulation of intracellular levels of NAD: A novel role for CD38

Pinar Aksoy, Thomas A. White, Michael Thompson, Eduardo Nunes Chini

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Nicotinamide adenine dinucleotide (NAD) plays key roles in many cellular functions. In addition to its well-known role in energy metabolism, NAD also plays a role in signal transduction, ageing, and cellular injury. NAD is also involved in many signal transduction pathways. Therefore, it is imperative to understand the mechanisms that control intracellular NAD levels. However, to date, the mechanisms that regulate intracellular levels of NAD have not been completely elucidated. CD38 is a multifunctional enzyme ubiquitously distributed in mammalian tissues. CD38 has been implicated as the enzyme responsible for the synthesis of the second messengers. However, its major enzymatic activity is the hydrolysis of NAD, in fact, CD38 will generate one molecule of cADPR for every 100 molecules of NAD hydrolyzed. To date, the role of CD38 as a modulator of levels of NAD has not been explored. We postulated that CD38 is the major NADase in mammalian cells and that it regulates intracellular NAD levels. In the current studies we examined the NADase activities and NAD levels in a variety of tissues from both wild-type and CD38 deficient mice. In accordance with our hypothesis, we found that tissue levels of NAD in CD38 deficient mice are 10- to 20-fold higher than in wild-type animals. In addition, NADase activity in the plasma membrane, mitochondria, sarcoplasmic reticulum, and nuclei is essentially absent in most tissues from CD38 deficient mice. These data support the novel concept that CD38 is a major regulator of cellular NAD levels. These findings have implications for understanding the mechanisms that regulate intracellular NAD levels and its role in energy homeostasis, signal transduction, and ageing.

Original languageEnglish (US)
Pages (from-to)1386-1392
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume345
Issue number4
DOIs
StatePublished - Jul 14 2006

Fingerprint

NAD
NAD+ Nucleosidase
Signal transduction
Tissue
Signal Transduction
Aging of materials
Cyclic ADP-Ribose
Multifunctional Enzymes
Mitochondria
Molecules
Wild Animals
Cell Aging
Sarcoplasmic Reticulum
Second Messenger Systems
Cell membranes
Energy Metabolism
Modulators
Hydrolysis
Animals
Homeostasis

Keywords

  • Brain
  • cADPR
  • Calcium
  • CD38
  • NAD

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Regulation of intracellular levels of NAD : A novel role for CD38. / Aksoy, Pinar; White, Thomas A.; Thompson, Michael; Chini, Eduardo Nunes.

In: Biochemical and Biophysical Research Communications, Vol. 345, No. 4, 14.07.2006, p. 1386-1392.

Research output: Contribution to journalArticle

Aksoy, Pinar ; White, Thomas A. ; Thompson, Michael ; Chini, Eduardo Nunes. / Regulation of intracellular levels of NAD : A novel role for CD38. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 345, No. 4. pp. 1386-1392.
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