title: L-tryptophan-kynurenine pathway metabolite 3-hydroxyanthranilic acid induces apoptosis in macrophage-derived cells under pathophysiological conditions.
abstract: Accumulation of L-kynurenine and 3-hydroxyanthranilic acid (3HAA) occurs in the monocyte-derived cells following immune stimulation, and may derive from L-tryptophan following induction of indoleamine-2,3-dioxygenase. In the present study, we evaluate the possibility that 3HAA acts as an endogenous inducer of monocyte/macrophage apoptosis. Supplementation with 200 microM of 3HAA, but not other L-tryptophan metabolites tested, significantly increased the number of apoptotic cells in both THP-1 and U937 cells. Catalase, superoxide dismutase and manganese ions markedly enhanced apoptosis in the presence of 3HAA in these cells. The present results suggest that 3HAA induces the macrophage/monocyte apoptosis under certain conditions, which may be relevant to pathophysiology of inflammatory conditions.
authors.affiliation: Department of Laboratory Medicine, Gifu University School of Medicine, Japan. morita@fmsrsa.fukui-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Takemura
authors.forename: N
authors.initials: N
authors.lastname: Maekawa
authors.forename: S
authors.initials: S
authors.lastname: Fujigaki
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: A
authors.initials: A
authors.lastname: Noma
authors.forename: M
authors.initials: M
authors.lastname: Seishima
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D015095:3-Hydroxyanthranilic Acid; D007737:Kynurenine; D014364:Tryptophan