title: Autophagy and mitochondrial alterations in human retinal pigment epithelial cells induced by ethanol: implications of 4-hydroxy-nonenal.
abstract: Retinal pigment epithelium has a crucial role in the physiology and pathophysiology of the retina due to its location and metabolism. Oxidative damage has been demonstrated as a pathogenic mechanism in several retinal diseases, and reactive oxygen species are certainly important by-products of ethanol (EtOH) metabolism. Autophagy has been shown to exert a protective effect in different cellular and animal models. Thus, in our model, EtOH treatment increases autophagy flux, in a concentration-dependent manner. Mitochondrial morphology seems to be clearly altered under EtOH exposure, leading to an apparent increase in mitochondrial fission. An increase in 2',7'-dichlorofluorescein fluorescence and accumulation of lipid peroxidation products, such as 4-hydroxy-nonenal (4-HNE), among others were confirmed. The characterization of these structures confirmed their nature as aggresomes. Hence, autophagy seems to have a cytoprotective role in ARPE-19 cells under EtOH damage, by degrading fragmented mitochondria and 4-HNE aggresomes. Herein, we describe the central implication of autophagy in human retinal pigment epithelial cells upon oxidative stress induced by EtOH, with possible implications for other conditions and diseases.
authors.affiliation: Department of Physiology, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Flores-Bellver
authors.affiliation: Department of Physiology, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Bonet-Ponce
authors.affiliation: Department of Physiology, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Barcia
authors.affiliation: Department of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutive Biology, University of Valencia, Valencia, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.affiliation: Department of Physiology, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Martinez-Gil
authors.affiliation: Department of Physiology, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Saez-Atienzar
authors.affiliation: Department of Physiology, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sancho-Pelluz
authors.affiliation: Neuropharmacology Group, Department of Medical Sciences, School of Medicine, University of Castilla la Mancha, IDINE, Albacete, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Jordan
authors.affiliation: Unit of Translational Neuropsychopharmacology, University of Castilla la Mancha and Albacete Hospital, Albacete, Spain.
authors.forename: M F
authors.initials: MF
authors.lastname: Galindo
authors.affiliation: Department of Physiology, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Romero
mesh_terms: D000447:Aldehydes / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012164:Retinal Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D000447:Aldehydes; D017382:Reactive Oxygen Species; D000431:Ethanol; C027576:4-hydroxy-2-nonenal