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KMID : 0043320080310030357
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Archives of Pharmacal Research
2008 Volume.31 No. 3 p.357 ~ p.363
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Inhibitory Effects of Crocetin On High Glucose-induced Apoptosis in Cultured Human Umbilical Vein Endothelial Cells and Its Mechanism
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Meng Lingdong
Cui Lianqun
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Abstract
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Dysfunction of endothelial cell is considered as a major cause of vascular complications in diabetes. Crocetin has been shown to have strong antioxidant activities. In present study, we tested whether crocetin inhibited high glucose-induced apoptosis in cultured human umbilical vein endothelial cells and to explore its possible mechanism. Exposure to high glucose (33 mM) for 72h induced a pronounced increase in apoptosis compared with normal glucose (5.5 mM),as evaluated by cell chromatin staining with Hoechst 33,258 and cell death detection ELISA. High glucose attenuated activation of Akt and endothelial nitric oxide synthase (eNOS). Crocetin (0.1 , 1.0 ) prevented high glucose-induced apoptosis, which correlates with the increase of activation of p-Akt, following the up-regulation of eNOS and NO production. Pretreatment with phosphatidylinositol 3’ kinase (PI3K) inhibitor LY294002 or eNOS inhibitor arginine methyl ester (LN or L-NAME) inhibited crocetin’ effect on p-Akt or eNOS, respectively. For the first time, results of our study suggest that crocetin inhibits high glucose-induced apoptosis, at least partly, via PI3K/Akt/eNOS pathway in and crocetin may exert a beneficial effect in preventing diabetes-associated cardiovascular complications.
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KEYWORD
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High glucose, Crocetin, Endothelial cell, Apoptosis, Akt, eNOS
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