title: Isorhapontigenin and resveratrol suppress oxLDL-induced proliferation and activation of ERK1/2 mitogen-activated protein kinases of bovine aortic smooth muscle cells.
abstract: The objective of our study was to compare the inhibitory effect of isorhapontigenin (ISO) and resveratrol, two natural antioxidants, on oxidized low-density lipoprotein (oxLDL)-induced proliferation of bovine aortic smooth muscle cells (BASMCs) and its relation to reactive oxygen species (ROS) generation and extracellular signal-regulated kinase 1/2 activation. The results showed that stimulation of oxLDL (50-150 microg/mL) for 48 hr induced a dose-dependent increase in cell number and incorporation of [3H]thymidine into DNA of BASMCs. Western blot analysis demonstrated that oxLDL (150 microg/mL) stimulated an evident phosphorylation of p42/44 MAP kinases in BASMCs. Incubation of BASMCs with oxLDL induced significant increase in ROS detected by using an oxidant-sensitive fluorescent probe of 2',7'-dichlorofluorescin diacetate. The level of H2O2 in the medium of cultured BASMCs also increased markedly. Preincubation of BASMCs with ISO and resveratrol significantly inhibited oxLDL-induced cell proliferation and incorporation of [3H]thymidine, and the phosphorylation of p42/44 MAP kinases in BASMCs as well. Furthermore, preincubation of BASMCs with ISO and resveratrol attenuated oxLDL-induced increases in ROS and H2O2 levels. The results suggested that oxLDL-induced acute formation of ROS and subsequent activation of redox-sensitive extracellular signal-regulated kinase 1/2 MAPK pathways, which might be important for mitogenic signaling of oxLDL in vascular smooth muscle cells. The inhibitory effect of ISO and resveratrol on oxLDL-induced mitogenesis of BASMCs might be taken through blocking the generation of ROS and activation of the ERKs pathway.
authors.affiliation: Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Liu
authors.forename: Gengtao
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001011:Aorta; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D008077:Lipoproteins, LDL; D013267:Stilbenes; C432307:isorhapontigenin; C099252:oxidized low density lipoprotein; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000077185:Resveratrol