Inhibition of the Induction of Nitric Oxide Synthase by Spermine Is Modulated by Aldehyde Dehydrogenase

G. J. Southan, Csaba Szabo, C. Thiemermann

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The observation that spermine inhibits the endotoxin (lipopolysaccharide; LPS) induced production of nitric oxide (NO) in macrophages has been ascribed to the conversion of SP to active metabolites by the action of enzymes, such as diamine oxidases, found, for example, in bovine sera. Inhibitory effect is also observed with the oxidised metabolite of spermine, spermine dialdehyde (SDA). Inhibition appears to be at the level of induction of the inducible isoform of NO synthase (iNOS). Here we show that the activity of endogenous aldehyde dehydrogenase present in the cells influences the degree of inhibition seen with either spermine or SDA. Most significantly, inhibition of aldehyde dehydrogenase activity greatly increases (100 fold) the ability of spermine to inhibit the production of nitrite by LPS-induced macrophages. This is presumably by preserving aldehyde metabolites of spermine and thus increasing its action on the induction of iNOS. Thus, inhibition of aldehyde dehydrogenase activity in vitro or in vivo may be a useful approach to enhance the inhibitory effect of polyamines or polyamine aldehydes on iNOS induction.

Original languageEnglish (US)
Pages (from-to)1638-1644
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume203
Issue number3
DOIs
StatePublished - Sep 30 1994
Externally publishedYes

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Aldehyde Dehydrogenase
Spermine
Nitric Oxide Synthase
Metabolites
Protein Isoforms
Macrophages
Polyamines
Aldehydes
Amine Oxidase (Copper-Containing)
Nitric Oxide Synthase Type II
Nitrites
Endotoxins
Lipopolysaccharides
Nitric Oxide
Enzymes
Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Inhibition of the Induction of Nitric Oxide Synthase by Spermine Is Modulated by Aldehyde Dehydrogenase. / Southan, G. J.; Szabo, Csaba; Thiemermann, C.

In: Biochemical and Biophysical Research Communications, Vol. 203, No. 3, 30.09.1994, p. 1638-1644.

Research output: Contribution to journalArticle

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