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D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway
Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregula...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917283/ https://www.ncbi.nlm.nih.gov/pubmed/33658920 http://dx.doi.org/10.3389/fphar.2020.556074 |
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author | Guo, Yansong Li, Wei Qian, Mingming Jiang, Ting Guo, Ping Du, Qian Lin, Na Xie, Xianwei Wu, Zhiyong Lin, Donghai Liu, Donghui |
author_facet | Guo, Yansong Li, Wei Qian, Mingming Jiang, Ting Guo, Ping Du, Qian Lin, Na Xie, Xianwei Wu, Zhiyong Lin, Donghai Liu, Donghui |
author_sort | Guo, Yansong |
collection | PubMed |
description | Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregulating heme oxygenase-1 (HO-1) expression and scavenging excessively generated reactive oxygen species (ROS). However, whether D-4F could ameliorate oxidative injuries in endothelial cells through suppressing ROS production remains unclear. In this study, a representative nonionic iodinated CM, iodixanol, was chosen for the in vitro and in vivo studies. Endothelial cell viability was assayed using micrographs, lactate dehydrogenase (LDH) activity, and cell counting kit-8 (CCK-8). Apoptosis was detected using flow cytometry analysis and caspase-3 activation. Endothelial inflammation was tested using monocyte adhesion assay and adhesion molecule expression. ROS production was detected by measuring the formation of lipid peroxidation malondialdehyde (MDA) through the thiobarbituric acid reactive substance (TBARS) assay. Peroxynitrite (ONOO⁻) formation was tested using the 3-nitrotyrosine ELISA kit. Iodixanol impaired cell viability, promoted vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression, and induced cell apoptosis in human umbilical vein endothelial cells (HUVECs). However, D-4F mitigated these injuries. Furthermore, iodixanol induced the phosphorylation of protein kinase C (PKC) beta II, p47, Rac1, and endothelial nitric oxide synthase (eNOS) at Thr495, which elicited ROS release and ONOO⁻ generation. D-4F inhibited NADPH oxidase (NOX) activation, ROS production, and ONOO⁻ formation via the AMP-activated protein kinase (AMPK)/PKC pathway. Additionally, after an intravascular injection of iodixanol in Sprague Dawley rats, iodixanol induced a remarkable inflammatory response in arterial endothelial cells, although significant apoptosis and morphological changes were not observed. D-4F alleviated the vessel inflammation resulting from iodixanol in vivo. Collectively, besides scavenging ROS, D-4F could also suppress ROS production and ONOO⁻ formation through the AMPK/PKC pathway, which ameliorated oxidative injuries in endothelial cells. Hence, D-4F might serve as a potential agent in preventing CI-AKI. |
format | Online Article Text |
id | pubmed-7917283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79172832021-03-02 D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway Guo, Yansong Li, Wei Qian, Mingming Jiang, Ting Guo, Ping Du, Qian Lin, Na Xie, Xianwei Wu, Zhiyong Lin, Donghai Liu, Donghui Front Pharmacol Pharmacology Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregulating heme oxygenase-1 (HO-1) expression and scavenging excessively generated reactive oxygen species (ROS). However, whether D-4F could ameliorate oxidative injuries in endothelial cells through suppressing ROS production remains unclear. In this study, a representative nonionic iodinated CM, iodixanol, was chosen for the in vitro and in vivo studies. Endothelial cell viability was assayed using micrographs, lactate dehydrogenase (LDH) activity, and cell counting kit-8 (CCK-8). Apoptosis was detected using flow cytometry analysis and caspase-3 activation. Endothelial inflammation was tested using monocyte adhesion assay and adhesion molecule expression. ROS production was detected by measuring the formation of lipid peroxidation malondialdehyde (MDA) through the thiobarbituric acid reactive substance (TBARS) assay. Peroxynitrite (ONOO⁻) formation was tested using the 3-nitrotyrosine ELISA kit. Iodixanol impaired cell viability, promoted vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression, and induced cell apoptosis in human umbilical vein endothelial cells (HUVECs). However, D-4F mitigated these injuries. Furthermore, iodixanol induced the phosphorylation of protein kinase C (PKC) beta II, p47, Rac1, and endothelial nitric oxide synthase (eNOS) at Thr495, which elicited ROS release and ONOO⁻ generation. D-4F inhibited NADPH oxidase (NOX) activation, ROS production, and ONOO⁻ formation via the AMP-activated protein kinase (AMPK)/PKC pathway. Additionally, after an intravascular injection of iodixanol in Sprague Dawley rats, iodixanol induced a remarkable inflammatory response in arterial endothelial cells, although significant apoptosis and morphological changes were not observed. D-4F alleviated the vessel inflammation resulting from iodixanol in vivo. Collectively, besides scavenging ROS, D-4F could also suppress ROS production and ONOO⁻ formation through the AMPK/PKC pathway, which ameliorated oxidative injuries in endothelial cells. Hence, D-4F might serve as a potential agent in preventing CI-AKI. Frontiers Media S.A. 2021-02-15 /pmc/articles/PMC7917283/ /pubmed/33658920 http://dx.doi.org/10.3389/fphar.2020.556074 Text en Copyright © 2021 Guo, Li, Qian, Jiang, Guo, Du, Lin, Xie, Wu, Lin and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Guo, Yansong Li, Wei Qian, Mingming Jiang, Ting Guo, Ping Du, Qian Lin, Na Xie, Xianwei Wu, Zhiyong Lin, Donghai Liu, Donghui D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway |
title | D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway |
title_full | D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway |
title_fullStr | D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway |
title_full_unstemmed | D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway |
title_short | D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway |
title_sort | d-4f ameliorates contrast media–induced oxidative injuries in endothelial cells via the ampk/pkc pathway |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917283/ https://www.ncbi.nlm.nih.gov/pubmed/33658920 http://dx.doi.org/10.3389/fphar.2020.556074 |
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