PMID- 10462479
OWN - NLM
STAT- MEDLINE
DCOM- 19991001
LR  - 20141120
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 262
IP  - 2
DP  - 1999 Aug 27
TI  - Nitric oxide inhibits ornithine decarboxylase by S-nitrosylation.
PG  - 355-8
AB  - Ornithine decarboxylase (ODC) is the initial enzyme in the polyamine synthetic
      pathway, and polyamines are required for cell proliferation. We have shown
      previously that nitric oxide (NO) inhibits ODC activity in Caco-2 cells and in
      crude cell lysate preparations. In this study we examined the mechanism by which 
      NO inhibits the activity of purified ODC. NO, in the form of S-nitrosocysteine
      (CysNO), S-nitrosoglutathione (GSNO), or 1,
      1-diethyl-2-hydroxy-2-nitroso-hydrazine (DEA/NO), inhibited enzyme activity in a 
      concentration-dependent manner. CysNO (1 microM) inhibited ODC activity by
      approximately 90% and 3 microM GSNO by more than 70%. DEA/NO was less potent,
      inhibiting enzyme activity by 70% at a concentration of 30 microM. Inhibition of 
      enzyme activity by CysNO, GSNO, or DEA/NO was reversible by addition of
      dithiothreitol or glutathione. Cuprous ion (Cu (I)) also reversed the inhibitory 
      effect of these NO donor agents. The data presented here support the hypothesis
      that NO inhibits ODC activity via S-nitrosylation of a critical cysteine
      residue(s) on ODC.
CI  - Copyright 1999 Academic Press.
FAU - Bauer, P M
AU  - Bauer PM
AD  - Department of Molecular and Medical Pharmacology, University of California-Los
      Angeles School of Medicine, Los Angeles, California, 90095-1735, USA.
FAU - Fukuto, J M
AU  - Fukuto JM
FAU - Buga, G M
AU  - Buga GM
FAU - Pegg, A E
AU  - Pegg AE
FAU - Ignarro, L J
AU  - Ignarro LJ
LA  - eng
GR  - HL35014/HL/NHLBI NIH HHS/United States
GR  - HL40922/HL/NHLBI NIH HHS/United States
GR  - HL58433/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Nitroso Compounds)
RN  - 0 (Ornithine Decarboxylase Inhibitors)
RN  - 0 (Sulfhydryl Compounds)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 789U1901C5 (Copper)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Catalytic Domain
MH  - Copper/pharmacology
MH  - Cysteine/*analogs & derivatives
MH  - Nitric Oxide/*pharmacology
MH  - Nitroso Compounds/*metabolism
MH  - Ornithine Decarboxylase/drug effects
MH  - *Ornithine Decarboxylase Inhibitors
MH  - Oxidation-Reduction
MH  - Sulfhydryl Compounds
EDAT- 1999/08/27 00:00
MHDA- 1999/08/27 00:01
CRDT- 1999/08/27 00:00
PHST- 1999/08/27 00:00 [pubmed]
PHST- 1999/08/27 00:01 [medline]
PHST- 1999/08/27 00:00 [entrez]
AID - 10.1006/bbrc.1999.1210 [doi]
AID - S0006-291X(99)91210-X [pii]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Aug 27;262(2):355-8. doi:
      10.1006/bbrc.1999.1210.