Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells
碩士 === 國立嘉義大學 === 生物科技研究所 === 92 === ABSTRACT Statins, HMG-CoA reductase inhibitors, in addition to cholesterol-lowering effects, have inhibitory effect in isoprenoid synthesis, which is required for the modification of Rho and increase NO production. However, under some conditions the st...
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ndltd-TW-092NCYU01110132015-10-13T13:04:19Z http://ndltd.ncl.edu.tw/handle/11544777211102514671 Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells 羥甲基戊二醯基CoA還原酶抑制劑對內皮細胞之細胞間附著因子基因誘導及氧化物形成之影響 Sheng-Ping Chang 張聖平 碩士 國立嘉義大學 生物科技研究所 92 ABSTRACT Statins, HMG-CoA reductase inhibitors, in addition to cholesterol-lowering effects, have inhibitory effect in isoprenoid synthesis, which is required for the modification of Rho and increase NO production. However, under some conditions the statins-increased NO production may react with superoxide to promote peroxynitrite formation, increasing the possibility of tissue injury. In this study, we examine the high dose treatment of statins on ICAM-1 gene induction in endothelial cells (ECs). Statins treated ECs increase intercellular ROS levels. ECs pretreated with lovastatin or mevastatin partially inhibit TNF-induced ICAM-1 gene expression, but they also promote the basal level of ICAM-1 gene expression. Pretreatment with antioxidant, NAC on cell, the lovastatin-induced ICAM-1 gene expression is reduced. Using mutation analysis of ICAM-1 promoter, we find lovastatin- increased ICAM-1 promoter activity is mediated through NF-kB activation. The induction of ICAM-1 promoter activity is reversed by the addition of mevalonate, GGPP or NO synthase inhibitor, L-NAME implicating that statins influence ICAM-1 gene expression via isoprenylation and NO production. These findings suggest that the statins may induce ICAM-1 gene expression via the increased NO production resulting of increase of intracellular ROS level. Being-Sun Wung Ping-Lin Ong 翁炳孫 翁秉霖 2004 學位論文 ; thesis 70 zh-TW |
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碩士 === 國立嘉義大學 === 生物科技研究所 === 92 === ABSTRACT
Statins, HMG-CoA reductase inhibitors, in addition to cholesterol-lowering effects, have inhibitory effect in isoprenoid synthesis, which is required for the modification of Rho and increase NO production. However, under some conditions the statins-increased NO production may react with superoxide to promote peroxynitrite formation, increasing the possibility of tissue injury. In this study, we examine the high dose treatment of statins on ICAM-1 gene induction in endothelial cells (ECs). Statins treated ECs increase intercellular ROS levels. ECs pretreated with lovastatin or mevastatin partially inhibit TNF-induced ICAM-1 gene expression, but they also promote the basal level of ICAM-1 gene expression. Pretreatment with antioxidant, NAC on cell, the lovastatin-induced ICAM-1 gene expression is reduced. Using mutation analysis of ICAM-1 promoter, we find lovastatin- increased ICAM-1 promoter activity is mediated through NF-kB activation. The induction of ICAM-1 promoter activity is reversed by the addition of mevalonate, GGPP or NO synthase inhibitor, L-NAME implicating that statins influence ICAM-1 gene expression via isoprenylation and NO production. These findings suggest that the statins may induce ICAM-1 gene expression via the increased NO production resulting of increase of intracellular ROS level.
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author2 |
Being-Sun Wung |
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Being-Sun Wung Sheng-Ping Chang 張聖平 |
author |
Sheng-Ping Chang 張聖平 |
spellingShingle |
Sheng-Ping Chang 張聖平 Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells |
author_sort |
Sheng-Ping Chang |
title |
Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells |
title_short |
Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells |
title_full |
Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells |
title_fullStr |
Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells |
title_full_unstemmed |
Influence of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ICAM-1 Gene Induction and the Formation of Oxidants in Endothelial Cells |
title_sort |
influence of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors on icam-1 gene induction and the formation of oxidants in endothelial cells |
publishDate |
2004 |
url |
http://ndltd.ncl.edu.tw/handle/11544777211102514671 |
work_keys_str_mv |
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