Inactivation of ribonucleotide reductase by nitric oxide.
Ribonucleotide reductase has been demonstrated to be inhibited by NO synthase product(s). The experiments reported here show that nitric oxide generated from sodium nitroprusside, S-nitrosoglutathione and the sydnonimine SIN-1 inhibits ribonucleotide reductase activity present in cytosolic extracts of TA3 mammary tumor cells. Stable derivatives of these nitric oxide donors were either inactive or much less inhibitory. EPR experiments show that the tyrosyl radical of the small subunit of E. Coli or mammalian ribonucleotide reductase is efficiently scavenged by these NO donors.
Lepoivre
M
M
URA CNRS 1116, Université Paris-Sud, Orsay, France.
Fieschi
F
F
Coves
J
J
Thelander
L
L
Fontecave
M
M
D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D026422:S-Nitrosoglutathione; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C002385:linsidomine; D008981:Molsidomine; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D012264:Ribonucleotide Reductases; D005978:Glutathione