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HIF-1 Has a Central Role in Caenorhabditis elegans Organismal Response to Selenium.
Romanelli-Credrez, Laura; Doitsidou, Maria; Alkema, Mark J; Salinas, Gustavo.
Afiliação
  • Romanelli-Credrez L; Laboratorio de Biología de Gusanos. Unidad Mixta, Departamento de Biociencias, Facultad de Química, Universidad de la República-Institut Pasteur de Montevideo, Montevideo, Uruguay.
  • Doitsidou M; Centre for Discovery Brain Sciences (CDBS), University of Edinburgh, Edinburgh, United Kingdom.
  • Alkema MJ; Neurobiology Department, University of Massachusetts Medical School, Worcester, MA, United States.
  • Salinas G; Laboratorio de Biología de Gusanos. Unidad Mixta, Departamento de Biociencias, Facultad de Química, Universidad de la República-Institut Pasteur de Montevideo, Montevideo, Uruguay.
Front Genet ; 11: 63, 2020.
Article em En | MEDLINE | ID: mdl-32161616
ABSTRACT
Selenium is a trace element for most organisms; its deficiency and excess are detrimental. Selenium beneficial effects are mainly due to the role of the 21st genetically encoded amino acid selenocysteine (Sec). Selenium also exerts Sec-independent beneficial effects. Its harmful effects are thought to be mainly due to non-specific incorporation in protein synthesis. Yet the selenium response in animals is poorly understood. In Caenorhabditis elegans, Sec is genetically incorporated into a single selenoprotein. Similar to mammals, a 20-fold excess of the optimal selenium requirement is harmful. Sodium selenite (Na2SeO3) excess causes development retardation, impaired growth, and neurodegeneration of motor neurons. To study the organismal response to selenium we performed a genetic screen for C. elegans mutants that are resistant to selenite. We isolated non-sense and missense egl-9/EGLN mutants that confer robust resistance to selenium. In contrast, hif-1/HIF null mutant was highly sensitive to selenium, establishing a role for this transcription factor in the selenium response. We showed that EGL-9 regulates HIF-1 activity through VHL-1, and identified CYSL-1 as a key sensor that transduces the selenium signal. Finally, we showed that the key enzymes involved in sulfide and sulfite stress (sulfide quinone oxidoreductase and sulfite oxidase) are not required for selenium resistance. In contrast, knockout strains in the persulfide dioxygenase ETHE-1 and the sulfurtransferase MPST-7 affect the organismal response to selenium. In sum, our results identified a transcriptional pathway as well as enzymes possibly involved in the organismal selenium response.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Article