Dihydromyricetin protects human umbilical vein endothelial cells from injury through ERK and Akt mediated Nrf2/HO-1 signaling pathway.

Abstract

Atherosclerosis-related cardiovascular disease is the predominant cause of death worldwide. Ox-LDL-induced vascular endothelial cell injury is a major factor in the pathogenesis of atherosclerosis. Dihydromyricetin (DMY) is a flavonoid extracted from vine tea that exerts multiple pharmacological activities, including cardio-protective, anti-tumor, and anti-oxidative effects. However, it is unreported that DMY shows protective effects on ox-LDL-induced endothelial cell injury. In this study, we used an ox-LDL injured human umbilical vein endothelial cell (HUVEC) in vitro model to explore the protective effects and mechanism of DMY. HUVECs were pretreatment with DMY and then exposed to ox-LDL, the cell viability was measured. Then, the anti-oxidative enzymes were tested by commercial kits and intracellular reactive oxygen species (ROS) was measured by flow cytometry, cell apoptosis was determined by Annexin-V/PI assay and apoptosis-related proteins were detected by western blot. Our results showed that DMY pretreatment provided cytoprotective effects by suppressing ox-LDL-induced endothelial cell apoptosis, mitochondrial membrane depolarization, caspase-3 activation, and modulation of oxidative enzymes, thereby inhibiting ROS generation. The anti-oxidative and anti-apoptotic effects of DMY were abrogated by the transfection of Nrf2 siRNAs and HO-1 inhibitor ZnPP. Furthermore, DMY might activate the Nrf2/HO-1 pathway through activation of the Akt and ERK1/2 pathways, as shown by the inhibition of Nrf2/HO-1 signaling by the inhibitors PD98059 or LY294002 and the transfection of ERK, Akt siRNAs. In this study, DMY protects HUVECs from ox-LDL-induced oxidative injury by activating Akt and ERK1/2, which subsequently activates Nrf2/HO-1 signaling, thereby up-regulating antioxidant enzymes and anti-apoptotic proteins.

• Authors: Yun Luo, Shan Lu, Xi Dong, Lijia Xu, Guibo Sun, Xiaobo Sun
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 22 Issue 8 Pg. 1013-1024 (08 2017) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 28612103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonols
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Protective Agents
• Reactive Oxygen Species
• HMOX1 protein, human
• Heme Oxygenase-1
• Oncogene Protein v-akt
• dihydromyricetin

Topics

• Apoptosis (drug effects)
• Atherosclerosis (drug therapy, genetics, pathology)
• Cell Survival (drug effects)
• Flavonols (administration & dosage)
• Flow Cytometry
• Heme Oxygenase-1 (genetics)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• MAP Kinase Signaling System (genetics)
• NF-E2-Related Factor 2 (genetics)
• Oncogene Protein v-akt (genetics)
• Oxidative Stress (drug effects)
• Protective Agents (administration & dosage)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)