The Role of MAP Kinasesand Akt, eNOS Phosphorylation Pathways in Oxysterols Induced Cytotoxicity in Human Umbilical Vein Endothelial Cells
| Autor: | 王智琦 |
|---|---|
| Rok vydání: | 2004 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 92 Oxidation products of cholesterol have been shown to be present in oxidized low density lipoprotein and in atherosclerotic lesions. Here we showed three oxysterols, Cholesterol-5a-6a-epoxide (Epoxide), 7-keto-cholesterol (7-Keto) and Cholesterol-3b-5a-6b-triol (Triol) induce cytotoxicity in human umbilical endothelial cells (HUVECs). And the cytotoxicity effect were regulated by MAP kinases, Akt, and eNOS phosphorylation through diversal pathways. Three oxysterols showed different mechanisms and dual aspects of regulation pathways, apoptosis or necrosis, and cell protection, in HUVECs. Epoxide did not cause cytotoxicity within 36 hours and showed the induction of cell protection proteins, ERK, Akt in HUVECs. Besides, Epoxide showed a feedback effect between ERK and eNOS, and thus it might show no cytotoxicity in HUVECs. This unique effect caused by Epoxide made it different from other two oxysterols. Triol showed obvious dual effects in HUVECs. One is cytotoxicity effect including apoptosis and necrosis. JNK, c-Jun, p-38 and caspase-3 were activated by Triol and those were believed to contribute the cytotoxicity. In addition, the generation of ROS also involved in Triol-induced cytotoxicity. Antioxidants such as N-acetylcystein (NAC), vitamin C and vitamin E could diminish the cytotoxicity of Triol. The other is the induction of cell protection proteins, like ERK and Akt. 7-Keto significantly induced apoptosis and JNK, c-Jun, p-38, caspase-3 activation in HUVECs. 7-Keto also activated ERK phosphorylation, and the p-JNK activation seems to contribute the beneficial effect in HUVECs. In summary, the role of oxysterols in HUVECs is controversial. We found that Triol and 7-Keto could induce cytotoxicity, but there is still a cell protection pathway going in the same time. Different with Triol and 7-keto, Epoxide only showed the beneficial effect in this study. The effect of oxysterols on HUVECs seems to be complicated and need further investigation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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