jf8b05025_si_001.pdf (43.25 kB)
Activation of Nrf2 by Phloretin Attenuates Palmitic Acid-Induced Endothelial Cell Oxidative Stress via AMPK-Dependent Signaling
journal contribution
posted on 2018-12-09, 00:00 authored by Qing Yang, Lin Han, Jie Li, Han Xu, Xinfeng Liu, Xinyu Wang, Chuanying Pan, Chuzhao Lei, Hong Chen, Xianyong LanPhloretin,
a dihydrochalcone structural flavonoid compound, possesses antioxidant
activity. In this study, we conducted studies to explore the function
of phloretin on high palmitic acid-induced oxidative stress in human
umbilical vein endothelial cells and investigated the potential mechanism
using ribonucleic acid sequencing (RNA-Seq). Our findings reveal that
phloretin significantly decreased the levels of intracellular reactive
oxygen species (ROS) and malondialdehyde (MDA), increased superoxide
dismutase (SOD) and glutathione peroxidase-1 (Gpx-1) activity, and
restored the loss of mitochondrial membrane potential (MMP). Next,
whole transcriptome analysis was performed using RNA-Seq The results
indicated more than 3000 differentially expressed genes (DEGs). Gene
Ontology analysis revealed that the DEGs were categorized functionally,
mainly by the biological processes, cell metabolism, and cellular
response to chemical stimulus. The Kyoto Encyclopedia of Genes and
Genomes indicated that they were mainly enriched in cAMP, apoptosis,
and cytoskeletal regulation signaling pathways. Furthermore, on the
basis of the results of RNA-Seq and Western blotting, our study verified
that phloretin upregulated the expression of p-Nrf2 and HO-1 by promoting
the phosphorylation of AMPK at Thr172 through activation
of liver kinase B1. In conclusion, phloretin attenuates PA-induced
oxidative stress in HUVECs via the AMPK/Nrf2 antioxidative pathway.
History
Usage metrics
Categories
Keywords
superoxide dismutasephloretin attenuates PA-induced oxidative stress3000 differentiallycytoskeletal regulationp-Nrf 2DEGROSantioxidant activityacid sequencingKyoto EncyclopediaGene Ontology analysisMDAcell metabolismglutathione peroxidasepalmitic acid-induced oxidative stressphloretin upregulatedflavonoid compoundliver kinase B 1.chemical stimulusMMPmitochondrial membraneHOHUVECAMPK-Dependent Signaling Phloretinintracellular reactive oxygen speciesThr 172SODumbilical veintranscriptome analysispathwayNrf 2Phloretin Attenuates Palmitic Acid-Induced Endothelial Cell Oxidative StressRNA-Seq
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC