Cubizolle 2020 J Cell Mol Med
|Cubizolle A, Cia D, Moine E, Jacquemot N, Guillou L, Rosell M, Angebault-Prouteau C, Lenaers G, Meunier I, Vercauteren J, Durand T, Crauste C, Brabet P (2020) Isopropyl-phloroglucinol-DHA protects outer retinal cells against lethal dose of all-trans-retinal. J Cell Mol Med 24:5057-69.|
Abstract: All-trans-retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11-cis-retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4-associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE). This A2E-accumulation presents as lipofuscin fluorescent pigment, and its photooxidation causes subsequent damage. Here we describe protection against a lethal dose of atRAL in both photoreceptors and RPE in primary cultures by a lipidic polyphenol derivative, an isopropyl-phloroglucinol linked to DHA, referred to as IP-DHA. Next, we addressed the cellular and molecular defence mechanisms in commonly used human ARPE-19 cells. We determined that both polyunsaturated fatty acid and isopropyl substituents bond to phloroglucinol are essential to confer the highest protection. IP-DHA responds rapidly against the toxicity of atRAL and its protective effect persists. This healthy effect of IP-DHA applies to the mitochondrial respiration. IP-DHA also rescues RPE cells subjected to the toxic effects of A2E after blue light exposure. Together, our findings suggest that the beneficial role of IP-DHA in retinal cells involves both anti-carbonyl and anti-oxidative capacities.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
• Keywords: All-trans-retinal, Bisretinoid A2E, Carbonyl stress, Isopropyl-phloroglucinol-DHA conjugate, Outer retina cells, Oxidative stress • Bioblast editor: Plangger M
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Rat Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, CIV, NS HRR: Oxygraph-2k