Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice
-
Published:2024-02-04
Issue:2
Volume:13
Page:201
-
ISSN:2076-3921
-
Container-title:Antioxidants
-
language:en
-
Short-container-title:Antioxidants
Author:
Moshtaghion Seyed Mohamadmehdi1, Caballano-Infantes Estefanía1, Plaza Reyes Álvaro1ORCID, Valdés-Sánchez Lourdes1ORCID, Fernández Patricia Gallego1, de la Cerda Berta1ORCID, Riga Maurizio S.1, Álvarez-Dolado Manuel1ORCID, Peñalver Pablo2ORCID, Morales Juan C.2ORCID, Díaz-Corrales Francisco J.1ORCID
Affiliation:
1. Department of Integrative Pathophysiology and Therapies, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Junta de Andalucía, CSIC, Universidad de Sevilla, Universidad Pablo de Olavide, Avda. Américo Vespucio 24, 41092 Seville, Spain 2. Department of Biochemistry and Molecular Pharmacology, Institute of Parasitology and Biomedicine López-Neyra (IPBLN), PTS-Granada, Avda. del Conocimiento, 17, 18016 Granada, Spain
Abstract
Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown that resveratrol (RSV) is a promising molecule that can mitigate PARP1 overactivity, but its low bioavailability is a limitation for medical use. This study examined the impact of a synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), in the 661W cell line against H2O2 oxidative stress and in rd10 mice. PIC-OCT possesses a better ADME profile than RSV. In response to H2O2, 661W cells pretreated with PIC-OCT preserved cell viability in more than 38% of cells by significantly promoting SIRT1 nuclear translocation, preserving NAD+/NADH ratio, and suppressing intracellular ROS formation. These effects result from expressing antioxidant genes, maintaining mitochondrial function, reducing PARP1 nuclear expression, and preventing AIF nuclear translocation. In rd10 mice, PIC-OCT inhibited PAR-polymer formation, increased SIRT1 expression, significantly reduced TUNEL-positive cells in the retinal outer nuclear layer, preserved ERGs, and enhanced light chamber activity (all p values < 0.05). Our findings corroborate that PIC-OCT protects photoreceptors by modulating the SIRT1/PARP1 axis in models of retinal degeneration.
Funder
Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional Junta de Andalucía
Subject
Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology
Reference108 articles.
1. Liu, W., Liu, S., Li, P., and Yao, K. (2022). Retinitis Pigmentosa: Progress in Molecular Pathology and Biotherapeutical Strategies. Int. J. Mol. Sci., 23. 2. Alternative Splicing and Retinal Degeneration;Liu;Clin. Genet.,2013 3. Mutations in Spliceosomal Proteins and Retina Degeneration;Arka;RNA Biol.,2017 4. Non-Syndromic Retinitis Pigmentosa;Verbakel;Prog. Retin. Eye Res.,2018 5. Yan, J., Chen, Y., Zhu, Y., and Paquet-Durand, F. (2021). Programmed Non-Apoptotic Cell Death in Hereditary Retinal Degeneration: Crosstalk between CGMP-Dependent Pathways and PARthanatos?. Int. J. Mol. Sci., 22.
|
|