PP2A alleviates oxidized LDL-induced endothelial dysfunction by regulating LOX-1/ROS/MAPK axis

Autor: Xiwen Liu, Dexin Yin, Yue Zhao, Kaicheng Xu, Guanghao Ren
Rok vydání: 2019
Předmět:
0301 basic medicine
MAPK/ERK pathway
MAP Kinase Signaling System
Lipoxygenase
macromolecular substances
environment and public health
030226 pharmacology & pharmacy
General Biochemistry
Genetics and Molecular Biology
Umbilical vein
03 medical and health sciences
0302 clinical medicine
Western blot
medicine
Human Umbilical Vein Endothelial Cells
Humans
Protein Phosphatase 2
General Pharmacology
Toxicology and Pharmaceutics
Endothelial dysfunction
Inhibitory effect
Inflammation
medicine.diagnostic_test
Dose-Response Relationship
Drug
Chemistry
General Medicine
Protein phosphatase 2
medicine.disease
Cell biology
Lipoproteins
LDL
enzymes and coenzymes (carbohydrates)
030104 developmental biology
embryonic structures
Molecular mechanism
lipids (amino acids
peptides
and proteins)
Endothelium
Vascular
Reactive Oxygen Species
Oxidized ldl
Zdroj: Life sciences. 243
ISSN: 1879-0631
Popis: Aims The purpose of this study is to investigate the effect of PP2A on the progression of AS and the special molecular mechanism. Main methods The expression of PP2A in Human umbilical vein endothelial cells (HUVECs) induced by different concentrations of Ox-LDL was measured by RT-PCR and Western blot. The binding activity of PP2A and LOX-1 was determined by CoIP assay. Western blot was used to measure the protein expression of VCAM-1, ICAM-1 and MCP-1. Key finding The results revealed that the expression of PP2A was decreased with the increase of Ox-LDL concentration in HUVECs. Overexpression of PP2A alleviated Ox-LDL-induced dysfunction and inflammatory response in HUVECs. The results of Co-immunoprecipitation (CoIP) showed that PP2A had direct effect on LOX-1, and PP2A inhibited the expression of LOX-1. In addition, overexpression of LOX-1 reversed the inhibitory effect of PP2A on Ox-LDL-induced dysfunction and inflammatory response in HUVECs. What is more, PP2A inhibited LOX-1/ROS/MAPK axis. Significance it suggests that PP2A alleviates Ox-LDL-induced dysfunction and inflammatory response of HUVECs potentially by regulating the LOX-1/ROS/MAPK axis，which suggests that PP2A has anti-inflammatory effect during the formation of as, and the molecular therapy of PP2A provides a theoretical basis.
Databáze: OpenAIRE
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