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SIRT1 participates in the response to methylglyoxal-dependent glycative stress in mouse oocytes and ovary.
Di Emidio, Giovanna; Santini, Silvano Junior; D'Alessandro, Anna Maria; Vetuschi, Antonella; Sferra, Roberta; Artini, Paolo Giovanni; Carta, Gaspare; Falone, Stefano; Amicarelli, Fernanda; Tatone, Carla.
Afiliación
  • Di Emidio G; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy; Infertility Service, San Salvatore Hospital, L'Aquila 67100, L'Aquila, Italy.
  • Santini SJ; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
  • D'Alessandro AM; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
  • Vetuschi A; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
  • Sferra R; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
  • Artini PG; Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynaecology, University of Pisa, Pisa, Italy.
  • Carta G; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy; Infertility Service, San Salvatore Hospital, L'Aquila 67100, L'Aquila, Italy.
  • Falone S; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
  • Amicarelli F; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy; Institute of Translational Pharmacology (IFT), National Council of Research (CNR), L'Aquila, Italy.
  • Tatone C; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy; Infertility Service, San Salvatore Hospital, L'Aquila 67100, L'Aquila, Italy. Electronic address: carla.tatone@univaq.it.
Biochim Biophys Acta Mol Basis Dis ; 1865(6): 1389-1401, 2019 06 01.
Article en En | MEDLINE | ID: mdl-30771486
Methylglyoxal (MG), a highly reactive dicarbonyl derived from metabolic processes, is the most powerful precursor of advanced glycation end products (AGEs). Glycative stress has been recently associated with ovarian dysfunctions in aging and PCOS syndrome. We have investigated the role of the NAD+-dependent Class III deacetylase SIRT1 in the adaptive response to MG in mouse oocytes and ovary. In mouse oocytes, MG induced up-expression of glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2) genes, components of the main MG detoxification system, whereas inhibition of SIRT1 by Ex527 or sirtinol reduced this response. In addition, the inhibition of SIRT1 worsened the effects of MG on oocyte maturation rates, while SIRT1 activation by resveratrol counteracted MG insult. Ovaries from female mice receiving 100 mg/kg MG by gastric administration for 28 days (MG mice) exhibited increased levels of SIRT1 along with over-expression of catalase, superoxide dismutase 2, SIRT3, PGC1α and mtTFA. Similar levels of MG-derived AGEs were observed in the ovaries from MG and control groups, along with enhanced protein expression of glyoxalase 1 in MG mice. Oocytes ovulated by MG mice exhibited atypical meiotic spindles, a condition predisposing to embryo aneuploidy. Our results from mouse oocytes revealed for the first time that SIRT1 could modulate MG scavenging by promoting expression of glyoxalases. The finding that up-regulation of glyoxalase 1 is associated with that of components of a SIRT1 functional network in the ovaries of MG mice provides strong evidence that SIRT1 participates in the response to methylglyoxal-dependent glycative stress in the female gonad.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oocitos / Ovario / Piruvaldehído / Productos Finales de Glicación Avanzada / Sirtuina 1 Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2019 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oocitos / Ovario / Piruvaldehído / Productos Finales de Glicación Avanzada / Sirtuina 1 Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2019 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos