Isorhapontigenin and resveratrol suppress oxLDL-induced proliferation and activation of ERK1/2 mitogen-activated protein kinases of bovine aortic smooth muscle cells.
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.
Liu
Yinglin
Y
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Liu
Gengtao
G
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*
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