title: Resveratrol suppresses oxidised low-density lipoprotein-induced macrophage apoptosis through inhibition of intracellular reactive oxygen species generation, LOX-1, and the p38 MAPK pathway.
abstract: OBJECTIVE
  Resveratrol (RSV) may have therapeutic potential for various diseases. Here we investigated the effect of RSV on oxidised low-density lipoprotein- (ox-LDL) induced apoptosis in RAW264.7 macrophages.
  
  
  METHODS
  Apoptosis of macrophages following incubation with ox-LDL (with or without RSV pre-treatment) was detected by flow cytometry. Western blotting was used to assess the protein expression of Bax, Bcl-2, and caspase-3 as well as ox-LDL receptor 1 (LOX-1) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Reactive oxygen species (ROS) generation was evaluated by 2', 7'-dichlorofluorescein diacetate, and JC-1 probe was used to determine the mitochondrial transmembrane potential of cells.
  
  
  RESULTS
  Ox-LDL significantly reduced viability and increased the rate of apoptosis (P < 0.05) in RAW264.7 cells. However, pre-treatment with RSV resulted in a remarkable decrease in this apoptotic effect. Moreover, ox-LDL caused the up-regulation of Bax and the down-regulation of Bcl-2, as well as the activation of caspase-3. Expression of LOX-1, phosphorylation of p38 MAPK, and intracellular ROS production also increased after ox-LDL stimulation. Strikingly, these effects were abolished by pre-treatment of cells with RSV.
  
  
  CONCLUSIONS
  RSV suppresses ox-LDL-induced macrophage apoptosis. These beneficial effects might be exerted through inhibition of ROS generation, LOX-1, and the p38 MAPK signalling pathway.
authors.affiliation: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Guo
authors.forename: Yang
authors.initials: Y
authors.lastname: Su
authors.forename: Baoxin
authors.initials: B
authors.lastname: Liu
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Shunping
authors.initials: S
authors.lastname: Zhou
authors.forename: Yawei
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D008077:Lipoproteins, LDL / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; C495138:Olr1 protein, mouse; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D013267:Stilbenes; C099252:oxidized low density lipoprotein; D048051:p38 Mitogen-Activated Protein Kinases; D000077185:Resveratrol