Characterization of NAD uptake in mammalian cells.
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.
Billington
Richard A
RA
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and the Drug and Food Biotechnology Center, Università del Piemonte Orientale, Via Bovio 6, Novara, Italy. billington@pharm.unipmn.it
Travelli
Cristina
C
Ercolano
Emanuela
E
Galli
Ubaldina
U
Roman
Cintia Blasi
CB
Grolla
Ambra A
AA
Canonico
Pier Luigi
PL
Condorelli
Fabrizio
F
Genazzani
Armando A
AA
D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D051379:Mice; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology; D009249:NADP / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010880:Piperidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000178:Acrylamides; C480543:N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide; D010880:Piperidines; D009243:NAD; D009249:NADP