Inhibition and ADP-ribose pyrophosphatase-I by nitric-oxide-generating systems: a mechanism linking nitric oxide to processes dependent on free ADP-ribose.
Rat liver ADP-ribose pyrophosphatase-I (ADPRibase-I; EC 3.6.1.13) hydrolyzes ADP-ribose with high specificity and a low Km. Thus it can participate in the control of free ADP-ribose and nonenzymatic ADP-ribosylation of proteins. Here we show that ADPRibase-I was inactivated by acidified nitrite, whereas sodium nitroprusside (SNP) or 3-morpholinosydnonimine (SIN-1) at pH 7.5 produced a dose- and time-dependent Km increase from 0.5 microM to 2 microM. The effects of SNP and SIN-1 depended on the presence and concentration of dithiothreitol, pointing to S-nitrosylation of enzyme thiols. It is suggested that, by inhibiting ADPRibase-I, NO can stimulate nonenzymatic ADP-ribosylation of targets susceptible to micromolar free ADP-ribose. This is discussed in relation to apparently contradictory earlier reports on the role of NO in the ADP-ribosylation of actin.
Ribeiro
J M
JM
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain.
Cameselle
J C
JC
Fernández
A
A
Canales
J
J
Pinto
R M
RM
Costas
M J
MJ
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors*; D051381:Rats; D012977:Sodium Nitrite / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D000246:Adenosine Diphosphate Ribose; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; C058796:ADP-ribose pyrophosphatase I; D011755:Pyrophosphatases; D012977:Sodium Nitrite