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KMID : 0857020050200010110
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Kosin Medical Journal
2005 Volume.20 No. 1 p.110 ~ p.119
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Induction of Heme Oxygenase-1 Expression by Rapamycin and Paclitaxel in Smooth Muscle and Endothelial Cells of Human and Rat
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Park Chul-Bo
Rhew Hyun-Yul
Chung Hun-Taeg
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Abstract
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Background: Both rapamycin and paclitaxel are currently being used in drug-eluting stent to block the proliferation of vascular endothelial and smooth muscle cells. Heme oxygenase-1 (HO-1) has also known to be anti-proliferative against vascular cells. In this study, it focused on the role of HO-1 in cytoprotection and antiproliferation of paclirtaxel.
Methods: Proliferation of cells and metabolic activity of HO-1 were evaluated with the tetrazolium-based assay. HO-1 protein expression was shown by western bolt analysis of vascular smooth muscle cells (VMSCs), or endothelial cells (ECs), using anti-HO-1 polyclonal antibody from untreated cells and cells exposed to rapamycin and paclitaxel. To determine whether the inhibition of paclitaxel on platelet-derived growth factor (PDGF)-detpendent proliferation may be mediated by its induction of HO-1, we exposed cells to paclitaxel, PDGF and ZnPP, an inhibitor of HO activity. Survival rate was checked to fine the anti-apototic effect of paclitaxel against tumor necrosis factor (TNF)-α-mediated apoptosis, in the presence or abscence of ZnPP.
Result: Rapamycin induces HO-1 protein in rat VSMCs and human ECs. Exposure of VSMCs to palcitaxel for 12 h resulted in a dose-dependent increase in HO-1 activity. Ten nM of paclitaxel led to a maximal expression of HO-1 protein at 12h after exposure. The addition of Znp abrogated the suppression effect of paclitaxel on PDGF-stimulated cell proliferation, and blocked paclitaxel-mediated suppression of TNF-α mediated apoptosis. Hemoglobin, a scavenger of CO, abrogated the paclitaxel induced cytoprotection.
Conclusion: Paclitaxel induced the expression of HO-1 gene in rat VSMCs and human ECs, in dose-dependent and time dependent manner, like rapamycin.
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KEYWORD
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rapamycin, paclitaxel, smooth muscle cell, endothelial cell, heme, oxygenase-1
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