Tyrosine aminotransferase is involved in the oxidative stress response by metabolizing meta-tyrosine in Caenorhabditis elegans.
J Biol Chem
; 294(24): 9536-9554, 2019 06 14.
Article
en En
| MEDLINE
| ID: mdl-31043480
ABSTRACT
Under oxidative stress conditions, hydroxyl radicals can oxidize the phenyl ring of phenylalanine, producing the abnormal tyrosine isomer meta-tyrosine (m-tyrosine). m-Tyrosine levels are commonly used as a biomarker of oxidative stress, and its accumulation has recently been reported to adversely affect cells, suggesting a direct role for m-tyrosine in oxidative stress effects. We found that the Caenorhabditis elegans ortholog of tyrosine aminotransferase (TATN-1)-the first enzyme involved in the metabolic degradation of tyrosine-is up-regulated in response to oxidative stress and directly activated by the oxidative stress-responsive transcription factor SKN-1. Worms deficient in tyrosine aminotransferase activity displayed increased sensitivity to multiple sources of oxidative stress. Biochemical assays revealed that m-tyrosine is a substrate for TATN-1-mediated deamination, suggesting that TATN-1 also metabolizes m-tyrosine. Consistent with a toxic effect of m-tyrosine and a protective function of TATN-1, tatn-1 mutant worms exhibited delayed development, marked reduction in fertility, and shortened lifespan when exposed to m-tyrosine. A forward genetic screen identified a mutation in the previously uncharacterized gene F01D4.5-homologous with human transcription factor 20 (TCF20) and retinoic acid-induced 1 (RAI1)-that suppresses the adverse phenotypes observed in m-tyrosine-treated tatn-1 mutant worms. RNA-Seq analysis of F01D4.5 mutant worms disclosed a significant reduction in the expression of specific isoforms of genes encoding ribosomal proteins, suggesting that alterations in protein synthesis or ribosome structure could diminish the adverse effects of m-tyrosine. Our findings uncover a critical role for tyrosine aminotransferase in the oxidative stress response via m-tyrosine metabolism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tirosina
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Factores de Transcripción
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Tirosina Transaminasa
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Regulación de la Expresión Génica
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Caenorhabditis elegans
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Estrés Oxidativo
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Proteínas de Caenorhabditis elegans
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Proteínas de Unión al ADN
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2019
Tipo del documento:
Article