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Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells

Diabetes-induced oxidative stress induces the development of vascular complications, which are significant causes of morbidity and mortality in diabetic patients. Among these, diabetic retinopathy (DR) is often caused by functional changes in the blood–retinal barrier (BRB) due to harmful oxidative...

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Autores principales: Bianchetti, Giada, Clementi, Maria Elisabetta, Sampaolese, Beatrice, Serantoni, Cassandra, Abeltino, Alessio, De Spirito, Marco, Sasson, Shlomo, Maulucci, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952658/
https://www.ncbi.nlm.nih.gov/pubmed/36829896
http://dx.doi.org/10.3390/antiox12020339
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author Bianchetti, Giada
Clementi, Maria Elisabetta
Sampaolese, Beatrice
Serantoni, Cassandra
Abeltino, Alessio
De Spirito, Marco
Sasson, Shlomo
Maulucci, Giuseppe
author_facet Bianchetti, Giada
Clementi, Maria Elisabetta
Sampaolese, Beatrice
Serantoni, Cassandra
Abeltino, Alessio
De Spirito, Marco
Sasson, Shlomo
Maulucci, Giuseppe
author_sort Bianchetti, Giada
collection PubMed
description Diabetes-induced oxidative stress induces the development of vascular complications, which are significant causes of morbidity and mortality in diabetic patients. Among these, diabetic retinopathy (DR) is often caused by functional changes in the blood–retinal barrier (BRB) due to harmful oxidative stress events in lipids, proteins, and DNA. Docosahexaenoic acid (DHA) has a potential therapeutic effect against hyperglycemia-induced oxidative damage and apoptotic pathways in the main constituents of BRB, retinal pigment epithelium cells (ARPE-19). Effective antioxidant response elicited by DHA is driven by the activation of the Nrf2/Nqo1 signaling cascade, which leads to the formation of NADH, a reductive agent found in the cytoplasm. Nrf2 also induces the expression of genes encoding enzymes involved in lipid metabolism. This study, therefore, aims at investigating the modulation of lipid metabolism induced by high-glucose (HG) on ARPE-19 cells through the integration of metabolic imaging and molecular biology to provide a comprehensive functional and molecular characterization of the mechanisms activated in the disease, as well the therapeutic role of DHA. This study shows that HG augments RPE metabolic processes by enhancing lipid metabolism, from fatty acid uptake and turnover to lipid biosynthesis and β-oxidation. DHA exerts its beneficial effect by ameliorating lipid metabolism and reducing the increased ROS production under HG conditions. This investigation may provide novel insight for formulating novel treatments for DR by targeting lipid metabolism pathways.
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spelling pubmed-99526582023-02-25 Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells Bianchetti, Giada Clementi, Maria Elisabetta Sampaolese, Beatrice Serantoni, Cassandra Abeltino, Alessio De Spirito, Marco Sasson, Shlomo Maulucci, Giuseppe Antioxidants (Basel) Article Diabetes-induced oxidative stress induces the development of vascular complications, which are significant causes of morbidity and mortality in diabetic patients. Among these, diabetic retinopathy (DR) is often caused by functional changes in the blood–retinal barrier (BRB) due to harmful oxidative stress events in lipids, proteins, and DNA. Docosahexaenoic acid (DHA) has a potential therapeutic effect against hyperglycemia-induced oxidative damage and apoptotic pathways in the main constituents of BRB, retinal pigment epithelium cells (ARPE-19). Effective antioxidant response elicited by DHA is driven by the activation of the Nrf2/Nqo1 signaling cascade, which leads to the formation of NADH, a reductive agent found in the cytoplasm. Nrf2 also induces the expression of genes encoding enzymes involved in lipid metabolism. This study, therefore, aims at investigating the modulation of lipid metabolism induced by high-glucose (HG) on ARPE-19 cells through the integration of metabolic imaging and molecular biology to provide a comprehensive functional and molecular characterization of the mechanisms activated in the disease, as well the therapeutic role of DHA. This study shows that HG augments RPE metabolic processes by enhancing lipid metabolism, from fatty acid uptake and turnover to lipid biosynthesis and β-oxidation. DHA exerts its beneficial effect by ameliorating lipid metabolism and reducing the increased ROS production under HG conditions. This investigation may provide novel insight for formulating novel treatments for DR by targeting lipid metabolism pathways. MDPI 2023-01-31 /pmc/articles/PMC9952658/ /pubmed/36829896 http://dx.doi.org/10.3390/antiox12020339 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bianchetti, Giada
Clementi, Maria Elisabetta
Sampaolese, Beatrice
Serantoni, Cassandra
Abeltino, Alessio
De Spirito, Marco
Sasson, Shlomo
Maulucci, Giuseppe
Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells
title Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells
title_full Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells
title_fullStr Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells
title_full_unstemmed Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells
title_short Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells
title_sort metabolic imaging and molecular biology reveal the interplay between lipid metabolism and dha-induced modulation of redox homeostasis in rpe cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952658/
https://www.ncbi.nlm.nih.gov/pubmed/36829896
http://dx.doi.org/10.3390/antiox12020339
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