Isopropyl‐phloroglucinol‐DHA protects outer retinal cells against lethal dose of all‐ trans ‐retinal - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Cellular and Molecular Medicine Année : 2020

Isopropyl‐phloroglucinol‐DHA protects outer retinal cells against lethal dose of all‐ trans ‐retinal

David Cia
Nathalie Jacquemot
  • Fonction : Auteur
Philippe Brabet

Résumé

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.
Fichier principal
Vignette du fichier
2020 Cubizolle J Cell Mol Med HAL.pdf (1.51 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence
Loading...

Dates et versions

hal-02593070 , version 1 (15-05-2020)

Licence

Identifiants

Citer

Aurelie Cubizolle, David Cia, Espérance Moine, Nathalie Jacquemot, Laurent Guillou, et al.. Isopropyl‐phloroglucinol‐DHA protects outer retinal cells against lethal dose of all‐ trans ‐retinal. Journal of Cellular and Molecular Medicine, 2020, 24 (9), pp.5057-5069. ⟨10.1111/jcmm.15135⟩. ⟨hal-02593070⟩
48 Consultations
132 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More