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  • Title: Isorhapontigenin and resveratrol suppress oxLDL-induced proliferation and activation of ERK1/2 mitogen-activated protein kinases of bovine aortic smooth muscle cells.
    Author: Liu Y, Liu G.
    Journal: Biochem Pharmacol; 2004 Feb 15; 67(4):777-85. PubMed ID: 14757178.
    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.
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