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KMID : 1034820130090030235
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Molecular & Cellular Toxicology
2013 Volume.9 No. 3 p.235 ~ p.241
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Methyl β-cyclodextrin activates eNOS-cGMP pathway in endothelial cells
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Park Kwang-Hyun
Kim Jong-Suk
Noh Eun-Mi
Yu Hong-Nu
Kim Sun-Young
Kim Sung-Zoo
Kim Soo-Mi
Chung Eun-Yong
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Abstract
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Cyclodextrins (CDs) have utility for solubilizing and stabilizing drugs. Recently CDs have been foused as therapeutics for neurodegenerative diseases. However, some CDs are toxic when administered parenterally. In this study, we investigated the effects of MβCD, a methylated form of β-CD, on endothelial cells using ECV 304 cells, a human endothelial cell line. Pretreatment of MβCD increased NO production in ECV 304 cells. MβCD induced an increase in phosphorylation of eNOS and in activities of adenylyl cyclase, guanylate cyclase, and their products, cAMP and cGMP, respectively. In addition, intraperitoneal administration of MβCD to rats (2 weeks) caused increase of serum nitrite level as well as decrease of blood pressure. These results suggest that MβCD has toxic effects against vascular tone through activation of eNOS-cGMP pathway in endothelial cells.
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KEYWORD
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MβCD, eNOS, cGMP, Nitric oxide, Blood pressure
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