3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-γ

Toshiko Morita, Kuniaki Saito, Masao Takemura, Naoya Maekawa, Suwako Fujigaki, Hidehiko Fujii, Hisayasu Wada, Shoji Takeuchi, Akio Noma, Mitsuru Seishima

Research output: Contribution to journalArticle

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Abstract

3-Hydroxyanthranilic acid (3-HAA), a metabolite of L-tryptophan, accumulates in monocyte-derived cells (THP-1), but not in other cell lines tested (MRC-9, H4, U373MG, Wil-NS), following immune stimulation that induces indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. We examined whether metabolites of the L-tryptophan-kynurenine pathway act to induce apoptosis in monocytes/macrophages. Of the L-tryptophan metabolites tested, only 3-HAA at a concentration of 200 μmol/L was found to induce apoptosis in THP-1 and U937 cells. The addition of ferrous or manganese ions further enhanced apoptosis and free radical formation by 3-HAA in these two types of cells. The apoptotic response induced by 3-HAA was significantly attenuated by the addition of antioxidant, α-tocopherol or Trolox (a water-soluble analogue of vitamin E), and the xanthine oxidase inhibitor, allopurinol. In addition, the 3-HAA-induced apoptotic response was slightly attenuated by catalase, but not by superoxide dismutase (SOD), indicating that generation of hydrogen peroxide is involved in this response. Interferon-γ (IFN-γ), an inducer of IDO, potently induced apoptosis in THP-1 cells, but not in U937 cells, in the presence of ferrous or manganese ions. This different susceptibility to apoptosis inducer between THP-I and U937 cells may depend on the capacity of the cells for 3-HAA synthesis following IDO induction by IFN-γ. Furthermore, apoptosis was suppressed by cycloheximide in THP-1 cells, suggesting that newly synthesized proteins may be essential for apoptotic events. These results suggest that 3-HAA induces apoptosis in monocytes/macrophages under inflammatory or other pathophysiological conditions.

Original languageEnglish
Pages (from-to)242-251
Number of pages10
JournalAnnals of Clinical Biochemistry
Volume38
Issue number3
DOIs
Publication statusPublished - 22-05-2001
Externally publishedYes

Fingerprint

3-Hydroxyanthranilic Acid
Metabolites
Tryptophan
Interferons
Monocytes
Apoptosis
Indoleamine-Pyrrole 2,3,-Dioxygenase
U937 Cells
Kynurenine
Macrophages
Manganese
Interferon Inducers
Ions
Allopurinol
Tocopherols
Xanthine Oxidase
Cycloheximide
Vitamin E
Catalase
Hydrogen Peroxide

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry

Cite this

Morita, Toshiko ; Saito, Kuniaki ; Takemura, Masao ; Maekawa, Naoya ; Fujigaki, Suwako ; Fujii, Hidehiko ; Wada, Hisayasu ; Takeuchi, Shoji ; Noma, Akio ; Seishima, Mitsuru. / 3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-γ. In: Annals of Clinical Biochemistry. 2001 ; Vol. 38, No. 3. pp. 242-251.
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title = "3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-γ",
abstract = "3-Hydroxyanthranilic acid (3-HAA), a metabolite of L-tryptophan, accumulates in monocyte-derived cells (THP-1), but not in other cell lines tested (MRC-9, H4, U373MG, Wil-NS), following immune stimulation that induces indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. We examined whether metabolites of the L-tryptophan-kynurenine pathway act to induce apoptosis in monocytes/macrophages. Of the L-tryptophan metabolites tested, only 3-HAA at a concentration of 200 μmol/L was found to induce apoptosis in THP-1 and U937 cells. The addition of ferrous or manganese ions further enhanced apoptosis and free radical formation by 3-HAA in these two types of cells. The apoptotic response induced by 3-HAA was significantly attenuated by the addition of antioxidant, α-tocopherol or Trolox (a water-soluble analogue of vitamin E), and the xanthine oxidase inhibitor, allopurinol. In addition, the 3-HAA-induced apoptotic response was slightly attenuated by catalase, but not by superoxide dismutase (SOD), indicating that generation of hydrogen peroxide is involved in this response. Interferon-γ (IFN-γ), an inducer of IDO, potently induced apoptosis in THP-1 cells, but not in U937 cells, in the presence of ferrous or manganese ions. This different susceptibility to apoptosis inducer between THP-I and U937 cells may depend on the capacity of the cells for 3-HAA synthesis following IDO induction by IFN-γ. Furthermore, apoptosis was suppressed by cycloheximide in THP-1 cells, suggesting that newly synthesized proteins may be essential for apoptotic events. These results suggest that 3-HAA induces apoptosis in monocytes/macrophages under inflammatory or other pathophysiological conditions.",
author = "Toshiko Morita and Kuniaki Saito and Masao Takemura and Naoya Maekawa and Suwako Fujigaki and Hidehiko Fujii and Hisayasu Wada and Shoji Takeuchi and Akio Noma and Mitsuru Seishima",
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Morita, T, Saito, K, Takemura, M, Maekawa, N, Fujigaki, S, Fujii, H, Wada, H, Takeuchi, S, Noma, A & Seishima, M 2001, '3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-γ', Annals of Clinical Biochemistry, vol. 38, no. 3, pp. 242-251. https://doi.org/10.1258/0004563011900461

3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-γ. / Morita, Toshiko; Saito, Kuniaki; Takemura, Masao; Maekawa, Naoya; Fujigaki, Suwako; Fujii, Hidehiko; Wada, Hisayasu; Takeuchi, Shoji; Noma, Akio; Seishima, Mitsuru.

In: Annals of Clinical Biochemistry, Vol. 38, No. 3, 22.05.2001, p. 242-251.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-γ

AU - Morita, Toshiko

AU - Saito, Kuniaki

AU - Takemura, Masao

AU - Maekawa, Naoya

AU - Fujigaki, Suwako

AU - Fujii, Hidehiko

AU - Wada, Hisayasu

AU - Takeuchi, Shoji

AU - Noma, Akio

AU - Seishima, Mitsuru

PY - 2001/5/22

Y1 - 2001/5/22

N2 - 3-Hydroxyanthranilic acid (3-HAA), a metabolite of L-tryptophan, accumulates in monocyte-derived cells (THP-1), but not in other cell lines tested (MRC-9, H4, U373MG, Wil-NS), following immune stimulation that induces indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. We examined whether metabolites of the L-tryptophan-kynurenine pathway act to induce apoptosis in monocytes/macrophages. Of the L-tryptophan metabolites tested, only 3-HAA at a concentration of 200 μmol/L was found to induce apoptosis in THP-1 and U937 cells. The addition of ferrous or manganese ions further enhanced apoptosis and free radical formation by 3-HAA in these two types of cells. The apoptotic response induced by 3-HAA was significantly attenuated by the addition of antioxidant, α-tocopherol or Trolox (a water-soluble analogue of vitamin E), and the xanthine oxidase inhibitor, allopurinol. In addition, the 3-HAA-induced apoptotic response was slightly attenuated by catalase, but not by superoxide dismutase (SOD), indicating that generation of hydrogen peroxide is involved in this response. Interferon-γ (IFN-γ), an inducer of IDO, potently induced apoptosis in THP-1 cells, but not in U937 cells, in the presence of ferrous or manganese ions. This different susceptibility to apoptosis inducer between THP-I and U937 cells may depend on the capacity of the cells for 3-HAA synthesis following IDO induction by IFN-γ. Furthermore, apoptosis was suppressed by cycloheximide in THP-1 cells, suggesting that newly synthesized proteins may be essential for apoptotic events. These results suggest that 3-HAA induces apoptosis in monocytes/macrophages under inflammatory or other pathophysiological conditions.

AB - 3-Hydroxyanthranilic acid (3-HAA), a metabolite of L-tryptophan, accumulates in monocyte-derived cells (THP-1), but not in other cell lines tested (MRC-9, H4, U373MG, Wil-NS), following immune stimulation that induces indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. We examined whether metabolites of the L-tryptophan-kynurenine pathway act to induce apoptosis in monocytes/macrophages. Of the L-tryptophan metabolites tested, only 3-HAA at a concentration of 200 μmol/L was found to induce apoptosis in THP-1 and U937 cells. The addition of ferrous or manganese ions further enhanced apoptosis and free radical formation by 3-HAA in these two types of cells. The apoptotic response induced by 3-HAA was significantly attenuated by the addition of antioxidant, α-tocopherol or Trolox (a water-soluble analogue of vitamin E), and the xanthine oxidase inhibitor, allopurinol. In addition, the 3-HAA-induced apoptotic response was slightly attenuated by catalase, but not by superoxide dismutase (SOD), indicating that generation of hydrogen peroxide is involved in this response. Interferon-γ (IFN-γ), an inducer of IDO, potently induced apoptosis in THP-1 cells, but not in U937 cells, in the presence of ferrous or manganese ions. This different susceptibility to apoptosis inducer between THP-I and U937 cells may depend on the capacity of the cells for 3-HAA synthesis following IDO induction by IFN-γ. Furthermore, apoptosis was suppressed by cycloheximide in THP-1 cells, suggesting that newly synthesized proteins may be essential for apoptotic events. These results suggest that 3-HAA induces apoptosis in monocytes/macrophages under inflammatory or other pathophysiological conditions.

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