Nitric oxide inhibits ornithine decarboxylase by S-nitrosylation

Philip M. Bauer, Jon M. Fukuto, Georgette M. Buga, Anthony Pegg, Louis J. Ignarro

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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 μM) inhibited ODC activity by approximately 90% and 3 μM GSNO by more than 70%. DEA/NO was less potent, inhibiting enzyme activity by 70% at a concentration of 30 μM. 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.

Original languageEnglish (US)
Pages (from-to)355-358
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume262
Issue number2
DOIs
StatePublished - Aug 27 1999

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Ornithine Decarboxylase
Nitric Oxide
Enzyme activity
hydrazine
Polyamines
Enzymes
S-Nitrosoglutathione
Enzyme inhibition
Caco-2 Cells
Nitric Oxide Donors
Dithiothreitol
Cell proliferation
Glutathione
Cysteine
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bauer, Philip M. ; Fukuto, Jon M. ; Buga, Georgette M. ; Pegg, Anthony ; Ignarro, Louis J. / Nitric oxide inhibits ornithine decarboxylase by S-nitrosylation. In: Biochemical and Biophysical Research Communications. 1999 ; Vol. 262, No. 2. pp. 355-358.
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Nitric oxide inhibits ornithine decarboxylase by S-nitrosylation. / Bauer, Philip M.; Fukuto, Jon M.; Buga, Georgette M.; Pegg, Anthony; Ignarro, Louis J.

In: Biochemical and Biophysical Research Communications, Vol. 262, No. 2, 27.08.1999, p. 355-358.

Research output: Contribution to journalArticle

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AU - Bauer, Philip M.

AU - Fukuto, Jon M.

AU - Buga, Georgette M.

AU - Pegg, Anthony

AU - Ignarro, Louis J.

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N2 - 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 μM) inhibited ODC activity by approximately 90% and 3 μM GSNO by more than 70%. DEA/NO was less potent, inhibiting enzyme activity by 70% at a concentration of 30 μM. 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.

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 μM) inhibited ODC activity by approximately 90% and 3 μM GSNO by more than 70%. DEA/NO was less potent, inhibiting enzyme activity by 70% at a concentration of 30 μM. 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.

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