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The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells.
Johansson, Ida; Monsen, Vivi Talstad; Pettersen, Kristine; Mildenberger, Jennifer; Misund, Kristine; Kaarniranta, Kai; Schønberg, Svanhild; Bjørkøy, Geir.
Afiliación
  • Johansson I; a Department of Laboratory Medicine ; Children's and Women's Health; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway.
  • Monsen VT; b Department of Technology ; University College of Sør-Trøndelag ; Trondheim , Norway.
  • Pettersen K; c Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine ; Norwegian University of Science and Technology ; Trondheim , Norway.
  • Mildenberger J; a Department of Laboratory Medicine ; Children's and Women's Health; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway.
  • Misund K; a Department of Laboratory Medicine ; Children's and Women's Health; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway.
  • Kaarniranta K; b Department of Technology ; University College of Sør-Trøndelag ; Trondheim , Norway.
  • Schønberg S; c Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine ; Norwegian University of Science and Technology ; Trondheim , Norway.
  • Bjørkøy G; b Department of Technology ; University College of Sør-Trøndelag ; Trondheim , Norway.
Autophagy ; 11(9): 1636-51, 2015.
Article en En | MEDLINE | ID: mdl-26237736
Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Autofagia / Ácidos Docosahexaenoicos / Pliegue de Proteína / Estrés Oxidativo / Citoprotección / Células Epiteliales / Factor 2 Relacionado con NF-E2 / Epitelio Pigmentado de la Retina Idioma: En Revista: Autophagy Año: 2015 Tipo del documento: Article País de afiliación: Noruega

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Autofagia / Ácidos Docosahexaenoicos / Pliegue de Proteína / Estrés Oxidativo / Citoprotección / Células Epiteliales / Factor 2 Relacionado con NF-E2 / Epitelio Pigmentado de la Retina Idioma: En Revista: Autophagy Año: 2015 Tipo del documento: Article País de afiliación: Noruega