The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.
Open accessAbstract
3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is markedly elevated under several pathological conditions, including Huntington disease and human immunodeficiency virus infection. Here we demonstrate that micromolar concentrations (1-100 microM) of 3-HK cause cell death in primary neuronal cultures prepared from rat striatum. The neurotoxicity of 3-HK was blocked by catalase and desferrioxamine but not by superoxide dismutase, indicating that the generation of hydrogen peroxide and hydroxyl radical is involved in the toxicity. Measurement of peroxide levels revealed that 3-HK caused intracellular accumulation of peroxide, which was largely attenuated by application of catalase. The peroxide accumulation and cell death caused by 1-10 microM 3-HK were also blocked by pretreatment with allopurinol or oxypurinol, suggesting that endogenous xanthine oxidase activity is involved in exacerbation of 3-HK neurotoxicity. Furthermore, NADPH diaphorase-containing neurons were spared from toxicity of these concentrations of 3-HK, a finding reminiscent of the pathological characteristics of several neurodegenerative disorders such as Huntington disease. These results suggest that 3-HK at pathologically relevant concentrations renders neuronal cells subject to oxidative stress leading to cell death, and therefore that this endogenous compound should be regarded as an important factor in pathogenesis of neurodegenerative disorders.
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Cites
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Cited by
Increased cortical kynurenate content in schizophrenia
Schwarcz, R., Rassoulpour, A., Wu, H.-Q., Medoff, D., Tamminga, C. A., & Roberts, R. C. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01078-2 · Cited by 590
Lovelace, M. D., Varney, B., Sundaram, G., Lennon, M. J., Lim, C. K., Jacobs, K., Guillemin, G. J., & Brew, B. J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.03.024 · Cited by 393
Tryptophan-kynurenine pathway is dysregulated in inflammation and immune activation
Zou, M.-H. (2015) · Frontiers in Bioscience · doi:10.2741/4363 · Cited by 361
The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity
Mbongue, J., Nicholas, D., Torrez, T., Kim, N.-S., Firek, A., & Langridge, W. (2015) · Vaccines · doi:10.3390/vaccines3030703 · Cited by 351
“Upon spontaneous auto-oxidation, 3-HAA produces reactive radical species, which, in turn, induce oxidative stress and apoptosis in neurons [31].”
BackgroundThe kynurenine pathway and neurodegenerative disease
Maddison, D. C., & Giorgini, F. (2015) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.03.002 · Cited by 309
Metadata
- Authors
- Okuda, S., Nishiyama, N., Saito, H., & Katsuki, H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-10-29
- Volume
- 93
- Issue
- 22
- Pages
- 12553-12558
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1992517022
- Cited by
- 301
- References
- 30
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
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- Okuda, S., Nishiyama, N., Saito, H., & Katsuki, H. (1996). Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.22.12553
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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