Antiproliferative Mechanisms of Probucol in H2O2-Stimulated Rat Aortic Smooth Muscle Cells
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    Abstract:

    Aim To investigate the antiproliferative mechanisms of probucol in rat vascular smooth muscle cells(VSMC) stimulated by H2O2. Methods Effects of probucol on cell cycle,DNA synthesis,cell proliferation and apoptosis in the presence of H2O2 were observed by means of MTT test,cell number count,3 H-TdR incorporation,FCM and RT-PCR. Results Probucol significantly inhibited proliferation and DNA synthesis of VSMC stimulated by H2O2.Cell number,A value and 3 H-TdR incorporation in probucol+H2O2 group were reduced by 46.9%,45.0%,and 39.5%,respectively,compared with H2O2 group(p<0.05).Probucol protected against H2O2-induced VSMC proliferation through inducing cell growth arrest at G0/G1 phase.H2O2 increased extracellular signal-regulated kinase-1(ERK-1) mRNA transcriptional levels by about 6 times and decreased mitogen-activated protein kinases phosphatase-1(MKP-1) mRNA by 82.2%,respectively,compared with controls.Probucol down-regulated the increase in H2O2-stimulated ERK-1 mRNA level and up-regulated MKP-1 mRNA level decreased by H2O2.Probucol induced apoptosis of VSMC under H2O2-stimulated condition. Conclusion Probucol suppresses H2O2-stimulated VSMC proliferation by inhibition of cell cycle progression via down-regulating ERK-1 mRNA transcriptional level,as well as inducton of apoptosis of VSMC.

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SHENG Lin, MA Cheng-En, HAO Lin, YUE Xin, and PAN Qi-Xing. Antiproliferative Mechanisms of Probucol in H2O2-Stimulated Rat Aortic Smooth Muscle Cells[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2007,15(9):678-682.

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History
  • Received:December 11,2006
  • Revised:June 02,2007
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