Extracellular NAD+ regulates intracellular free calcium concentration in human monocytes.
Ca(2+) ions play a critical role in the biochemical cascade of signal transduction pathways, leading to the activation of immune cells. In the present study, we show that the exposure of freshly isolated human monocytes to NAD(+) results in a rapid concentration-dependent elevation of [Ca(2+)](i) (intracellular free Ca(2+) concentration) caused by the influx of extracellular Ca(2+). NAD(+) derivatives containing a modified adenine or nicotinamide ring failed to trigger a Ca(2+) increase. Treating monocytes with ADPR (ADP-ribose), a major degradation product of NAD(+), also resulted in a rise in [Ca(2+)](i). Selective inhibition of CD38, an NAD-glycohydrolase that generates free ADPR from NAD(+), does not abolish the effect of NAD(+), excluding the possibility that NAD(+) might act via ADPR. The NAD(+)-induced Ca(2+) response was prevented by the prior addition of ADPR and vice versa, indicating that both compounds share some mechanisms mediating the rise in [Ca(2+)](i). NAD(+), as well as ADPR, were ineffective when applied following ATP, suggesting that ATP controls events that intersect with NAD(+) and ADPR signalling.
Gerth
Anja
A
Department of Immunobiology, Institute of Zoology, University of Leipzig, Liebigstrasse 18, D-04103 Leipzig, Germany.
Nieber
Karen
K
Oppenheimer
Norman J
NJ
Hauschildt
Sunna
S
D036541:ADP-ribosyl Cyclase / Q000037:antagonists & inhibitors; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000502:physiology; D015703:Antigens, CD; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000378:metabolism*; D009243:NAD / Q000031:analogs & derivatives / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D000255:Adenosine Triphosphate; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium