Tags

Type your tag names separated by a space and hit enter

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.
Autophagy. 2015; 11(9):1636-51.A

Abstract

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.

Authors+Show Affiliations

a Department of Laboratory Medicine ; Children's and Women's Health; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway. b Department of Technology ; University College of Sør-Trøndelag ; Trondheim , Norway. c Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine ; Norwegian University of Science and Technology ; Trondheim , Norway.a Department of Laboratory Medicine ; Children's and Women's Health; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway.a Department of Laboratory Medicine ; Children's and Women's Health; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway. b Department of Technology ; University College of Sør-Trøndelag ; Trondheim , Norway. c Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine ; Norwegian University of Science and Technology ; Trondheim , Norway.b Department of Technology ; University College of Sør-Trøndelag ; Trondheim , Norway. c Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine ; Norwegian University of Science and Technology ; Trondheim , Norway. d Department of Cancer Research and Molecular Medicine ; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway.d Department of Cancer Research and Molecular Medicine ; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway. e KG Jebsen Center for Myeloma Research; Norwegian University of Science and Technology ; Trondheim , Norway.f Department of Ophthalmology ; Institute of Clinical Medicine; University of Eastern Finland ; Kuopio , Finland. g Department of Ophthalmology ; Kuopio University Hospital ; Kuopio , Finland.a Department of Laboratory Medicine ; Children's and Women's Health; Faculty of Medicine; Norwegian University of Science and Technology ; Trondheim , Norway.b Department of Technology ; University College of Sør-Trøndelag ; Trondheim , Norway. c Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine ; Norwegian University of Science and Technology ; Trondheim , Norway.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26237736

Citation

Johansson, Ida, et al. "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." Autophagy, vol. 11, no. 9, 2015, pp. 1636-51.
Johansson I, Monsen VT, Pettersen K, et al. 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. Autophagy. 2015;11(9):1636-51.
Johansson, I., Monsen, V. T., Pettersen, K., Mildenberger, J., Misund, K., Kaarniranta, K., Schønberg, S., & Bjørkøy, G. (2015). 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. Autophagy, 11(9), 1636-51. https://doi.org/10.1080/15548627.2015.1061170
Johansson I, et al. 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. Autophagy. 2015;11(9):1636-51. PubMed PMID: 26237736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Johansson,Ida, AU - Monsen,Vivi Talstad, AU - Pettersen,Kristine, AU - Mildenberger,Jennifer, AU - Misund,Kristine, AU - Kaarniranta,Kai, AU - Schønberg,Svanhild, AU - Bjørkøy,Geir, PY - 2015/8/4/entrez PY - 2015/8/4/pubmed PY - 2016/6/21/medline KW - AA KW - DHA KW - HMOX1 KW - LC3B KW - MAP1LC3B KW - NFE2L2 KW - NRF2 KW - OA KW - PUFA KW - ROS KW - SQSTM1 KW - antioxidants KW - autophagy KW - omega-3 KW - p62 SP - 1636 EP - 51 JF - Autophagy JO - Autophagy VL - 11 IS - 9 N2 - 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. SN - 1554-8635 UR - https://www.unboundmedicine.com/medline/citation/26237736/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_ L2 - http://www.tandfonline.com/doi/full/10.1080/15548627.2015.1061170 DB - PRIME DP - Unbound Medicine ER -