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

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.Electronic supplementary materialThe online version of this article (10.1186/s12986-019-0338-7) contains supplementary material, which is available to authorized users.

Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB

“…Moreover, the concentrations applied in our study were in line with some previously published works [8, 36]. Autophagy is a cellular housekeeping process involved in the turnover of cytoplasmic organelles and proteins through a lysosome-dependent degradation process, and it plays a critical role in cancers, neurodegenerative disorders, and cardiovascular diseases [37–39]. Autophagy has been described as a major cytoprotective mechanism associated with phytochemicals [40].…”

[Retracted] Natural Antioxidants Improve the Vulnerability of Cardiomyocytes and Vascular Endothelial Cells under Stress Conditions: A Focus on Mitochondrial Quality Control

“…Moreover, it inhibits excessive mitochondrial fission, restores the MMP, and inhibits apoptosis in HUVECs. The regulatory effect of resveratrol on mitochondrial fission/fusion and its protective effect on endothelial cells were affected by siRNA interference of TyrRS and PARP1 , indicating that resveratrol regulates mitochondrial fission/fusion through TyrRS-PARP1 signalling [ 63 ].…”

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

“…Moreover, our discovery of TyrRS being a biologically significant and physiologically relevant target of RSV that facilitates the conversion of trans-RSV to cis-RSV suggests that the cis-isomer of RSV is also a major isomer that evokes protective stress response. Other recent studies have also confirmed the TyrRS-PARP1 signaling in mediating the protective effects of RSV [120,229,296,[432][433][434]. However, there are still critical gaps in our knowledge.…”

“…Activation of SIRT1 sensitizes neurons to oxidative stress [221,222] and inhibits neurogenesis [223] while RSV protects neurons against oxidative stress [224,225] and enhances neurogenesis [226,227]. Similarly, activation of SIRT1 promotes mitochondrial fission [228], and treatment with RSV rather enhances mitochondrial fusion [229]. Similarly, although brain-specific activation of SIRT1 drives anxiety and exploratory drive [48,230], RSV rather protects against autistic features [231][232][233][234].…”

“…Hence, it is speculated that the name "resveratrol": was created based on its chemical structure and the source of the plant used for its isolation (a resorcinol derivative or polyphenol in resin from a Veratrum species). Despite being a protective molecule in plants, the ingestion of RSV could also evoke similar protective stress responses in animals and was widely expected to overcome stressful/harmful conditions [9], including auto-immune disorders [10]. Unfortunately, despite being one of the widely studied small molecules, the in vivo animal models of diseases and human clinical studies using RSV brought out inconclusive results [11,12], indicating our understanding of the mechanism of action of natural RSV is not yet complete.…”