Efecto de los polifenoles sobre la respuesta a estrés de retículo endoplasmático en células hepáticas. Estudios in vitro e in vivo

• Autores: Cristina Rojas Domínguez
• Directores de la Tesis: Miquel Mulero Abellán (dir. tes.)
• Lectura: En la Universitat Rovira i Virgili ( España ) en 2013
• Idioma: catalán
• Tribunal Calificador de la Tesis: Xavier Remesar Betlloch (presid.), Maria Cinta Blade Segarra (secret.), Francesc Puiggròs Llavinés (voc.)
• Calificación: Apto Cum Laude
• Materias:
  • Química
    • Bioquímica
      • Biología molecular
  • Ciencias de la vida
    • Biología molecular
  • Ciencias médicas
    • Ciencias de la nutrición
      • Nutrientes
      • Enfermedades de la nutrición
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Endoplasmic reticulum (ER) stress response, also called UPR (Unfolded Protein Response), has an important role either in liver lipid metabolism and hepatic steatosis, which is the hepatic manifestation of the Metabolic Síndrome (MS). It has been reported that some polyphenols reduce lipid acumulation in vitro and in vivo. In contrast, saturated fatty acids rich-diet promotes UPR activation and hepatic steatosis in vivo. Due to the intersection of the ER stress signaling pathways and hepatic lipid metabolism, we hypothesized that the polyphenols ability to reduce lipid accumulation induced by saturated fatty acids treatment could be mediated by a reduction in the UPR in vivo and in vitro. The results suggest that grape seed proantocianidins extract (GSPE) and docosahexaenoic acid (DHA) are able to reduce ER stress in a rat model of diet-induced obesity. Surprisingly, in HepG2 cells acute treatments, resveratrol (RSV) enhanced both toxicity and apoptosis induced by palmitate. Elucidation of the molecular mechanisms that participate in this effect led us to study the membrane saturation and, specifically, the enzyme SCD1 as an important target in the action of this polyphenol. The impairment in the capacity to “mobilize” the cellular saturation activated UPR mechanisms and the related apoptosis. In contrast to what obtained in acute treatments, the chronic RSV preconditioning has a protective effect in palmitate-induced ER stress in HepG2 cells due to a decrease in pro-apoptotic molecules (PUMA, CHOP) expression and, thus, an improvement in the adaptive ability of these cells against stronger ER stress inducers.