Characterization of NAD uptake in mammalian cells

J Biol Chem. 2008 Mar 7;283(10):6367-74. doi: 10.1074/jbc.M706204200. Epub 2008 Jan 7.

Abstract

Recent evidence has shown that NAD(P) plays a variety of roles in cell-signaling processes. Surprisingly, the presence of NAD(P) utilizing ectoenzymes suggests that NAD(P) is present extracellularly. Indeed, nanomolar concentrations of NAD have been found in plasma and other body fluids. Although very high concentrations of NAD have been shown to enter cells, it is not known whether lower, more physiological concentrations are able to be taken up. Here we show that two mammalian cell types are able to transport low NAD concentrations effectively. Furthermore, extracellular application of NAD was able to counteract FK866-induced cell death and restore intracellular NAD(P) levels. We propose that NAD uptake may play a role in physiological NAD homeostasis.

MeSH terms

  • Acrylamides / pharmacology
  • Animals
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Humans
  • K562 Cells
  • Mice
  • NAD / metabolism*
  • NAD / pharmacology
  • NADP / metabolism*
  • NIH 3T3 Cells
  • Piperidines / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Acrylamides
  • N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide
  • Piperidines
  • NAD
  • NADP