期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 602, 期 2-3, 页码 277-282出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.11.026
关键词
P-glycoprotein; Insulin; Rat brain microvessel endothelial cell; Blood-brain barrier
资金
- National Natural Sciences Foundation of China [30672499]
- Project of Innovation in Graduate Education, Jiangsu Province [2006]
Our previous study showed that insulin restored impaired function and expression of P-glycoprotein in diabetic blood-brain barrier, and further study showed that insulin up-regulated P-glycoprotein expression and function in normal blood-brain barrier, so insulin might be one of the factors that regulated the function and expression of P-glycoprotein in blood-brain barrier of diabetes. In this study, the intracellular pathways that insulin regulated the P-glycoprotein were investigated using primarily cultured rat brain microvessel endothelial cells model. The rat brain microvessel endothelial cells were incubated in normal culture medium containing 50 mU/l insulin and different concentrations of inhibitors for 72 h. The P-glycoprotein function and expression in the rat brain microvessel endothelial cells were assessed using the uptake of P-glycoprotein substrate rhodamine 123 and western blot assay, respectively. It was found that treatment of 50 mU/l insulin significantly increased P-glycoprotein function and expression in rat brain microvessel endothelial cells. This induced effect was blocked by insulin receptor antibody, insulin receptor tyrosine kinase inhibitor I-OMe-AG538, PKC inhibitor chelerythrine and NF-kappa B inhibitor pyrrolidine dithiocarbamate ammonium (PDTC). But this induced effect was not inhibited by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002. These results indicated that insulin regulated P-glycoprotein function and expression through signal transduction pathways involving activation of PKC/NF-kappa B but not PI3K/Akt pathway (C) 2008 Elsevier B.V. All rights reserved.
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