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Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells

BACKGROUND: Endoplasmic reticulum stress (ERS) is part of the cardiovascular pathological processes, including atherosclerosis. Nuclear factor IA (NFIA) influences atherosclerosis development; however, its effects on ERS remain unknown. This study investigated the effect of NFIA on oxidized low-dens...

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Autores principales: Zhou, Zhenyu, Chen, Yu, Ni, Wei, Liu, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373224/
https://www.ncbi.nlm.nih.gov/pubmed/30721172
http://dx.doi.org/10.12659/MSM.912132
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author Zhou, Zhenyu
Chen, Yu
Ni, Wei
Liu, Tao
author_facet Zhou, Zhenyu
Chen, Yu
Ni, Wei
Liu, Tao
author_sort Zhou, Zhenyu
collection PubMed
description BACKGROUND: Endoplasmic reticulum stress (ERS) is part of the cardiovascular pathological processes, including atherosclerosis. Nuclear factor IA (NFIA) influences atherosclerosis development; however, its effects on ERS remain unknown. This study investigated the effect of NFIA on oxidized low-density lipoprotein (ox-LDL)-induced ERS and apoptosis in endothelial cells. MATERIAL/METHODS: Ox-LDL was used to induce lipotoxicity in human umbilical vein endothelial cells (HUVECs) to establish an in vitro oxidative injury model transfected with pcDNA3.0-NFIA. The cytotoxic response was detected using an assay to determine the release of lactate dehydrogenase (LDH). Morphological changes in cell apoptosis were detected using Hoechst 33258 staining. The proportion of apoptotic cells, releases of reactive oxygen species (ROS), and mitochondrial membrane potential (ΔΨm) were determined using flow cytometry. The expression levels of apoptosis- and ERS-related molecules were detected through Western blotting. RESULTS: NFIA expression was downregulated in the in vitro oxidative cell-injury model. Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis, decrease in ROS levels, and loss of ΔΨm. Overexpression of NFIA remarkably inhibited ERS and mitochondrial-mediated apoptosis induced by ox-LDL in HUVECs by reversing the effect of ox-LDL on the expression of JNK1, p-JNK1, CHOP, Cyt C, and Bax. CONCLUSIONS: These results demonstrated that NFIA might have beneficial effects in the prevention of ox-LDL-induced ERS and apoptosis in vascular endothelial cells. This study provided new insights into the mechanism of atherosclerosis.
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spelling pubmed-63732242019-02-15 Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells Zhou, Zhenyu Chen, Yu Ni, Wei Liu, Tao Med Sci Monit Lab/In Vitro Research BACKGROUND: Endoplasmic reticulum stress (ERS) is part of the cardiovascular pathological processes, including atherosclerosis. Nuclear factor IA (NFIA) influences atherosclerosis development; however, its effects on ERS remain unknown. This study investigated the effect of NFIA on oxidized low-density lipoprotein (ox-LDL)-induced ERS and apoptosis in endothelial cells. MATERIAL/METHODS: Ox-LDL was used to induce lipotoxicity in human umbilical vein endothelial cells (HUVECs) to establish an in vitro oxidative injury model transfected with pcDNA3.0-NFIA. The cytotoxic response was detected using an assay to determine the release of lactate dehydrogenase (LDH). Morphological changes in cell apoptosis were detected using Hoechst 33258 staining. The proportion of apoptotic cells, releases of reactive oxygen species (ROS), and mitochondrial membrane potential (ΔΨm) were determined using flow cytometry. The expression levels of apoptosis- and ERS-related molecules were detected through Western blotting. RESULTS: NFIA expression was downregulated in the in vitro oxidative cell-injury model. Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis, decrease in ROS levels, and loss of ΔΨm. Overexpression of NFIA remarkably inhibited ERS and mitochondrial-mediated apoptosis induced by ox-LDL in HUVECs by reversing the effect of ox-LDL on the expression of JNK1, p-JNK1, CHOP, Cyt C, and Bax. CONCLUSIONS: These results demonstrated that NFIA might have beneficial effects in the prevention of ox-LDL-induced ERS and apoptosis in vascular endothelial cells. This study provided new insights into the mechanism of atherosclerosis. International Scientific Literature, Inc. 2019-02-05 /pmc/articles/PMC6373224/ /pubmed/30721172 http://dx.doi.org/10.12659/MSM.912132 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Zhou, Zhenyu
Chen, Yu
Ni, Wei
Liu, Tao
Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells
title Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells
title_full Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells
title_fullStr Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells
title_full_unstemmed Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells
title_short Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells
title_sort upregulation of nuclear factor ia suppresses oxidized low-density lipoprotein-induced endoplasmic reticulum stress and apoptosis in human umbilical vein endothelial cells
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373224/
https://www.ncbi.nlm.nih.gov/pubmed/30721172
http://dx.doi.org/10.12659/MSM.912132
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