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Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment
Diabetic retinopathy (DR) is an important microvascular complication of diabetes and one of the leading causes of blindness in developed countries. Two large clinical studies showed that fenofibrate, a peroxisome proliferator-activated receptor type α (PPAR-α) agonist, reduces DR progression. We eva...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464418/ https://www.ncbi.nlm.nih.gov/pubmed/32764528 http://dx.doi.org/10.3390/antiox9080712 |
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author | Hsu, Ying-Jung Lin, Chao-Wen Cho, Sheng-Li Yang, Wei-Shiung Yang, Chung-May Yang, Chang-Hao |
author_facet | Hsu, Ying-Jung Lin, Chao-Wen Cho, Sheng-Li Yang, Wei-Shiung Yang, Chung-May Yang, Chang-Hao |
author_sort | Hsu, Ying-Jung |
collection | PubMed |
description | Diabetic retinopathy (DR) is an important microvascular complication of diabetes and one of the leading causes of blindness in developed countries. Two large clinical studies showed that fenofibrate, a peroxisome proliferator-activated receptor type α (PPAR-α) agonist, reduces DR progression. We evaluated the protective effects of fenofibrate on retinal/choroidal vascular endothelial cells under oxidative stress and investigated the underlying mechanisms using RF/6A cells as the model system and paraquat (PQ) to induce oxidative stress. Pretreatment with fenofibrate suppressed reactive oxygen species (ROS) production, decreased cellular apoptosis, diminished the changes in the mitochondrial membrane potential, increased the mRNA levels of peroxiredoxin (Prx), thioredoxins (Trxs), B-cell lymphoma 2 (Bcl-2), and Bcl-xl, and reduced the level of B-cell lymphoma 2-associated X protein (Bax) in PQ-stimulated RF/6A cells. Western blot analysis revealed that fenofibrate repressed apoptosis through cytosolic and mitochondrial apoptosis signal-regulated kinase-1 (Ask)-Trx-related signaling pathways, including c-Jun amino-terminal kinase (JNK) phosphorylation, cytochrome c release, caspase 3 activation, and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage. These protective effects of fenofibrate on RF/6A cells may be attributable to its anti-oxidative ability. Our research suggests that fenofibrate could serve as an effective adjunct therapy for ocular oxidative stress-related disorders, such as DR. |
format | Online Article Text |
id | pubmed-7464418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74644182020-09-04 Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment Hsu, Ying-Jung Lin, Chao-Wen Cho, Sheng-Li Yang, Wei-Shiung Yang, Chung-May Yang, Chang-Hao Antioxidants (Basel) Article Diabetic retinopathy (DR) is an important microvascular complication of diabetes and one of the leading causes of blindness in developed countries. Two large clinical studies showed that fenofibrate, a peroxisome proliferator-activated receptor type α (PPAR-α) agonist, reduces DR progression. We evaluated the protective effects of fenofibrate on retinal/choroidal vascular endothelial cells under oxidative stress and investigated the underlying mechanisms using RF/6A cells as the model system and paraquat (PQ) to induce oxidative stress. Pretreatment with fenofibrate suppressed reactive oxygen species (ROS) production, decreased cellular apoptosis, diminished the changes in the mitochondrial membrane potential, increased the mRNA levels of peroxiredoxin (Prx), thioredoxins (Trxs), B-cell lymphoma 2 (Bcl-2), and Bcl-xl, and reduced the level of B-cell lymphoma 2-associated X protein (Bax) in PQ-stimulated RF/6A cells. Western blot analysis revealed that fenofibrate repressed apoptosis through cytosolic and mitochondrial apoptosis signal-regulated kinase-1 (Ask)-Trx-related signaling pathways, including c-Jun amino-terminal kinase (JNK) phosphorylation, cytochrome c release, caspase 3 activation, and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage. These protective effects of fenofibrate on RF/6A cells may be attributable to its anti-oxidative ability. Our research suggests that fenofibrate could serve as an effective adjunct therapy for ocular oxidative stress-related disorders, such as DR. MDPI 2020-08-05 /pmc/articles/PMC7464418/ /pubmed/32764528 http://dx.doi.org/10.3390/antiox9080712 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hsu, Ying-Jung Lin, Chao-Wen Cho, Sheng-Li Yang, Wei-Shiung Yang, Chung-May Yang, Chang-Hao Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment |
title | Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment |
title_full | Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment |
title_fullStr | Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment |
title_full_unstemmed | Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment |
title_short | Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment |
title_sort | protective effect of fenofibrate on oxidative stress-induced apoptosis in retinal–choroidal vascular endothelial cells: implication for diabetic retinopathy treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464418/ https://www.ncbi.nlm.nih.gov/pubmed/32764528 http://dx.doi.org/10.3390/antiox9080712 |
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