Abstract
Background/aimsOxidative 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.MethodsHUVECs 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.ResultsRSV 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.ConclusionsRSV attenuated endothelial oxidative injury by regulating mitochondrial fusion via TyrRS-PARP1 signaling pathway.
Highlights
Atherosclerosis (AS) is a chronic disease characterized by the accumulation of lipids and fibrous plaques in the large arteries, which leads to hardening and narrowing of the arteries and causes most cardiovascular diseases (CVDs) [1]
At the concentration of 200 μM, the cell viability declined to (46.9 ± 1.88) % compared with the control group (p < 0.01), which indicated that 200 μM was around the IC50 of palmitic acid (PA) to human umbilical vein endothelial cells (HUVECs)
RSV attenuates PA-induced oxidative stress in HUVECs associated with Tyrosyl transfer-RNA synthetase (TyrRS) and poly (ADP-ribose) polymerase 1 (PARP1) To elucidate the effects of RSV on PA-induced oxidative stress in HUVECs, we examined the intracellular reactive oxygen species (ROS) level in HUVECs
Summary
Atherosclerosis (AS) is a chronic disease characterized by the accumulation of lipids and fibrous plaques in the large arteries, which leads to hardening and narrowing of the arteries and causes most cardiovascular diseases (CVDs) [1]. The endothelial wall is the first barrier to prevent the oxidative stress damage. Mitochondria, the major ROS generation sites, are motile organelles that are present in the mammalian cell and display a continuous cycle of fission and fusion, known as mitochondrial dynamics [4]. These mitochondrial dynamics are mediated by extensive protein machinery and, in combination with mitochondrial swelling/shrinking and removal of damaged mitochondria by mitophagy, determine net mitochondrial morphology. During the last decade, accumulating evidence suggests that cellular and mitochondrial redox homeostasis is linked to mitochondrial dynamics, mediated by extensive protein machinery and determining net mitochondrial morphology [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
