Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway

Abstract Background/aims Oxidative stress-induced damage in endothelial cells is a crucial initiator of atherosclerosis (AS), which is highly related to excessive reactive oxygen species (ROS) and mitochondrial dynamics. Resveratrol (RSV) exerts beneficial effects against endothelial oxidative injur...

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Main Authors: Jining Yang, Xi Zhou, Xianglong Zeng, Ou Hu, Long Yi, Mantian Mi
Format: Article
Language:English
Published: BMC 2019-01-01
Series:Nutrition & Metabolism
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12986-019-0338-7
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author Jining Yang
Xi Zhou
Xianglong Zeng
Ou Hu
Long Yi
Mantian Mi
author_facet Jining Yang
Xi Zhou
Xianglong Zeng
Ou Hu
Long Yi
Mantian Mi
author_sort Jining Yang
collection DOAJ
description Abstract Background/aims Oxidative stress-induced damage in endothelial cells is a crucial initiator of atherosclerosis (AS), which is highly related to excessive reactive oxygen species (ROS) and mitochondrial dynamics. Resveratrol (RSV) exerts beneficial effects against endothelial oxidative injury, while the underlying mechanisms have not been fully elucidated. Thus, we aimed to explore the role of mitochondria dynamics during the anti-oxidative activities of RSV in palmitic acid (PA)-stimulated human umbilical vein endothelial cells (HUVECs) and to verify whether tyrosyl transfer- RNA synthetase (TyrRS) and poly (ADP-ribose) polymerase 1 (PARP1) are targeted during this process. Methods HUVECs were exposed to 200 μM of PA for 16 h before treated with 10 μM of RSV for 8 h. Cell viability was detected using Cell counting kit-8 (CCK-8) assay. The intracellular ROS level and mitochondria membrane potential (MMP) were measured using microplate reader and flow cytometry. The malondialdehyde and superoxide dismutase were measured using the microplate reader. The mitochondrial morphology and fusion process was observed under transmission electron microscopy and confocal microscopy. TyrRS and PARP1 were knocked down with the specific small interference RNAs (siRNA), and the protein expressions of TyrRS, PARP1, and mitochondrial fusion proteins (MFN1, MFN2, and OPA1) were measured by western blot. Results RSV treatment suppressed the PA-induced injuries in HUVECs, including the damage to cell viability, oxidative stress, and loss of MMP. Additionally, RSV improved the protein levels of MFN1, MFN2, and OPA1 as well as inhibited the PA-induced fragmentation of mitochondria. However, the effects of RSV on oxidative stress and mitochondrial fusion were abolished by the pretreatment of siRNAs of TyrRS and PARP1, indicating that these effects of RSV were dependent on the TyrRS-PARP1 pathway. Conclusions RSV attenuated endothelial oxidative injury by regulating mitochondrial fusion via TyrRS-PARP1 signaling pathway.
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spelling doaj.art-c30c102cf4db4ce3a6b0379f7674ccf12022-12-21T23:00:19ZengBMCNutrition & Metabolism1743-70752019-01-0116111310.1186/s12986-019-0338-7Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathwayJining Yang0Xi Zhou1Xianglong Zeng2Ou Hu3Long Yi4Mantian Mi5Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical UniversityResearch Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical UniversityResearch Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical UniversityResearch Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical UniversityResearch Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical UniversityResearch Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical UniversityAbstract Background/aims Oxidative stress-induced damage in endothelial cells is a crucial initiator of atherosclerosis (AS), which is highly related to excessive reactive oxygen species (ROS) and mitochondrial dynamics. Resveratrol (RSV) exerts beneficial effects against endothelial oxidative injury, while the underlying mechanisms have not been fully elucidated. Thus, we aimed to explore the role of mitochondria dynamics during the anti-oxidative activities of RSV in palmitic acid (PA)-stimulated human umbilical vein endothelial cells (HUVECs) and to verify whether tyrosyl transfer- RNA synthetase (TyrRS) and poly (ADP-ribose) polymerase 1 (PARP1) are targeted during this process. Methods HUVECs were exposed to 200 μM of PA for 16 h before treated with 10 μM of RSV for 8 h. Cell viability was detected using Cell counting kit-8 (CCK-8) assay. The intracellular ROS level and mitochondria membrane potential (MMP) were measured using microplate reader and flow cytometry. The malondialdehyde and superoxide dismutase were measured using the microplate reader. The mitochondrial morphology and fusion process was observed under transmission electron microscopy and confocal microscopy. TyrRS and PARP1 were knocked down with the specific small interference RNAs (siRNA), and the protein expressions of TyrRS, PARP1, and mitochondrial fusion proteins (MFN1, MFN2, and OPA1) were measured by western blot. Results RSV treatment suppressed the PA-induced injuries in HUVECs, including the damage to cell viability, oxidative stress, and loss of MMP. Additionally, RSV improved the protein levels of MFN1, MFN2, and OPA1 as well as inhibited the PA-induced fragmentation of mitochondria. However, the effects of RSV on oxidative stress and mitochondrial fusion were abolished by the pretreatment of siRNAs of TyrRS and PARP1, indicating that these effects of RSV were dependent on the TyrRS-PARP1 pathway. Conclusions RSV attenuated endothelial oxidative injury by regulating mitochondrial fusion via TyrRS-PARP1 signaling pathway.http://link.springer.com/article/10.1186/s12986-019-0338-7Endothelial cellsAtherosclerosisResveratrolMitochondrial dynamicsTyrRSPARP1
spellingShingle Jining Yang
Xi Zhou
Xianglong Zeng
Ou Hu
Long Yi
Mantian Mi
Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway
Nutrition & Metabolism
Endothelial cells
Atherosclerosis
Resveratrol
Mitochondrial dynamics
TyrRS
PARP1
title Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway
title_full Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway
title_fullStr Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway
title_full_unstemmed Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway
title_short Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway
title_sort resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via tyrrs parp1 pathway
topic Endothelial cells
Atherosclerosis
Resveratrol
Mitochondrial dynamics
TyrRS
PARP1
url http://link.springer.com/article/10.1186/s12986-019-0338-7
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