Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB
碩士 === 中國醫藥大學 === 物理治療學系復健科學碩士班 === 98 === Abstract Background: Oxidized low-density lipoprotein (oxLDL) is a proatherogenic molecule that accumulates in the vascular wall and contributes to the pathogenesis of vascular dysfunction. LOX-1, a lectin-like oxLDL receptor, is responsible for binding and...
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ndltd-TW-098CMCH53530042015-10-28T04:07:29Z http://ndltd.ncl.edu.tw/handle/24048051824372443439 Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB 銀杏萃取物調降LOX-1所媒介之內皮細胞傷:活性氧自由基,MAPK 激酶及NF-κB之角色 Kai-ling Chen 陳凱玲 碩士 中國醫藥大學 物理治療學系復健科學碩士班 98 Abstract Background: Oxidized low-density lipoprotein (oxLDL) is a proatherogenic molecule that accumulates in the vascular wall and contributes to the pathogenesis of vascular dysfunction. LOX-1, a lectin-like oxLDL receptor, is responsible for binding and uptake of oxLDL in endothelial cells. It has been well documented that the activation of LOX-1 can stimulate the formation of ROS and initiate a cascade of redox-sensitive singnaling events. Ginkgo biloba extract (GbE), extracted from the leaves of the Ginkgo biloba tree, has been well known about its benefits in cardiovascular and neurological systems. In this study, we hypothesize that GbE protects against oxLDL-induced endothelial dysfunction by modulating the LOX-1-mediated signaling pathway. Methods: In this study, incubation of primary human umbilical vein endothelial cell culture (HUVECs) were pretreated with GbE 12.5, 25, 50, 100 ?慊/ml for 2 hours, and then incubated with oxLDL (130 ?慊/ml) for an additional 24 hours. Results: The results of this study showed that GbE or DPI (a well-known inhibitor of NADPH oxidase) reduced ROS production and up-regulation of LOX-1 caused by oxLDL. We also found that oxLDL increased action of p47phox and Rac-1, and the subsequent induction of ROS generation; nevertheless, ROS generation was significantly decreased in cells pretreated with GbE or anti-LOX-1 monoclonal antibody. Following, oxLDL up-regulated inducible NO synthase (iNOS),thereby augmenting the formation of NO and protein nitrosylation. Furthermore, oxLDL also increased p38MAPK phosphorylation and decreased the phosphorylation of the Akt, AMPK, eNOS with maximal induction at about 30 min, and activated the NF-κB-mediated inflammatory, redox-sensitive signaling. Pretreatment with GbE; however, exerted significant cytoprotective effects in all events. Conclusion: These data suggest that GbE inhibits the oxLDL-induced LOX-1-mediated signaling pathway, at least in part, by inhibiting NADPH oxidase and consequent ROS-enhanced LOX-1 expression, which contributes to further ROS generation and the subsequent suppressing the release of NO by down-regulating eNOS and activation of NF-κB via the p38MAPK pathway. Results from this study may provide insight into a possible molecular mechanism by which GbE prevent oxLDL-induced endothelial dysfunction. Keywords: Oxidized low density lipoprotein; Lectin-like ox-LDL receptor-1; Reactive oxygen species; endothelial cells; Ginkgo biloba extract 李信達 2010 學位論文 ; thesis 41 zh-TW |
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碩士 === 中國醫藥大學 === 物理治療學系復健科學碩士班 === 98 === Abstract
Background: Oxidized low-density lipoprotein (oxLDL) is a proatherogenic molecule that accumulates in the vascular wall and contributes to the pathogenesis of vascular dysfunction. LOX-1, a lectin-like oxLDL receptor, is responsible for binding and uptake of oxLDL in endothelial cells. It has been well documented that the activation of LOX-1 can stimulate the formation of ROS and initiate a cascade of redox-sensitive singnaling events. Ginkgo biloba extract (GbE), extracted from the leaves of the Ginkgo biloba tree, has been well known about its benefits in cardiovascular and neurological systems. In this study, we hypothesize that GbE protects against oxLDL-induced endothelial dysfunction by modulating the LOX-1-mediated signaling pathway. Methods: In this study, incubation of primary human umbilical vein endothelial cell culture (HUVECs) were pretreated with GbE 12.5, 25, 50, 100 ?慊/ml for 2 hours, and then incubated with oxLDL (130 ?慊/ml) for an additional 24 hours. Results: The results of this study showed that GbE or DPI (a well-known inhibitor of NADPH oxidase) reduced ROS production and up-regulation of LOX-1 caused by oxLDL. We also found that oxLDL increased action of p47phox and Rac-1, and the subsequent induction of ROS generation; nevertheless, ROS generation was significantly decreased in cells pretreated with GbE or anti-LOX-1 monoclonal antibody. Following, oxLDL up-regulated inducible NO synthase (iNOS),thereby augmenting the formation of NO and protein nitrosylation. Furthermore, oxLDL also increased p38MAPK phosphorylation and decreased the phosphorylation of the Akt, AMPK, eNOS with maximal induction at about 30 min, and activated the NF-κB-mediated inflammatory, redox-sensitive signaling. Pretreatment with GbE; however, exerted significant cytoprotective effects in all events. Conclusion: These data suggest that GbE inhibits the oxLDL-induced LOX-1-mediated signaling pathway, at least in part, by inhibiting NADPH oxidase and consequent ROS-enhanced LOX-1 expression, which contributes to further ROS generation and the subsequent suppressing the release of NO by down-regulating eNOS and activation of NF-κB via the p38MAPK pathway. Results from this study may provide insight into a possible molecular mechanism by which GbE prevent oxLDL-induced endothelial dysfunction.
Keywords: Oxidized low density lipoprotein; Lectin-like ox-LDL receptor-1; Reactive oxygen species; endothelial cells; Ginkgo biloba extract
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author2 |
李信達 |
author_facet |
李信達 Kai-ling Chen 陳凱玲 |
author |
Kai-ling Chen 陳凱玲 |
spellingShingle |
Kai-ling Chen 陳凱玲 Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB |
author_sort |
Kai-ling Chen |
title |
Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB |
title_short |
Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB |
title_full |
Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB |
title_fullStr |
Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB |
title_full_unstemmed |
Ginkgo biloba extract down-regulateLOX-1-mediated endothelial dysfunction:Role of ROS ,MAPK and NF-κB |
title_sort |
ginkgo biloba extract down-regulatelox-1-mediated endothelial dysfunction:role of ros ,mapk and nf-κb |
publishDate |
2010 |
url |
http://ndltd.ncl.edu.tw/handle/24048051824372443439 |
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