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dc.contributor.authorJohansson, Ida
dc.contributor.authorMonsen, Vivi Anita Talstad
dc.contributor.authorPettersen, Kristine
dc.contributor.authorMildenberger, Jennifer
dc.contributor.authorMisund, Kristine
dc.contributor.authorKaarniranta, Kai
dc.contributor.authorSchønberg, Svanhild Margrethe Arentz
dc.contributor.authorBjørkøy, Geir
dc.identifier.citationAutophagy. 2015, 11 (9), 1636-1651.nb_NO
dc.description.abstractAccumulation 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.nb_NO
dc.publisherTaylor & Francisnb_NO
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.titleThe marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cellsnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcode© Ida Johansson, Vivi Talstad Monsen, Kristine Pettersen, Jennifer Mildenberger, Kristine Misund, Kai Kaarniranta, Svanhild Schønberg, and Geir Bjørkøy. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.nb_NO
cristin.unitnameInstitutt for laboratoriemedisin, barne- og kvinnesykdommer
cristin.unitnameInstitutt for kreftforskning og molekylær medisin
cristin.unitnameFakultet for teknologi

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Navngivelse-Ikkekommersiell 4.0 Internasjonal
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