Insulin suppresses the expression and function of breast cancer resistance protein in primary cultures of rat brain microvessel endothelial cells
Insulin suppresses the expression and function of breast cancer resistance protein in primary cultures of rat brain microvessel endothelial cells
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胰岛素抑制大鼠脑微血管内皮细胞原代培养物中乳腺癌耐药蛋白的表达和功能
DOI：
10.1016/s1734-1140(11)70515-1
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发表时间：
2011-03
影响因子：
4.4
通讯作者：
Xie, Lin
中科院分区：
文献类型：
--
作者：
Liu, Xiang;Jing, Xin-yue;Jin, Shi;Li, Yang;Liu, Li;Yu, Yun-li;Liu, Xiao-dong;Xie, Lin
本研究利用原代培养的大鼠脑微血管内皮细胞(RBMECs)作为血脑屏障(BBB)的体外模型，探讨胰岛素在调节乳腺癌耐药蛋白(BCRP)功能和表达中的作用。分别用哌唑嗪摄取实验和Western印迹分析检测BCRP的功能和表达。据指出，rBMECs对哌唑嗪的摄取依赖于时间、浓度和温度。BCRP抑制剂新诺比星和甲磺酸伊马替尼以浓度依赖的方式显著增加细胞对哌唑嗪的摄取。细胞与糖尿病大鼠血清孵育72h，建立糖尿病体外模型。我们发现在糖尿病大鼠血清中孵育的rBMECs对哌唑嗪的摄取是正常大鼠血清中的39.8%，而胰岛素治疗逆转了这一下降。进一步的结果表明，胰岛素以浓度依赖的方式下调rBMECs中BCRP的功能和表达。胰岛素受体抗体的治疗消除了胰岛素诱导的BCRP功能和表达的下调。这些结果表明，胰岛素抑制了原代培养的rBMEC中BCRPs的功能和表达。
The aim of this study was to investigate the role of insulin in the regulation of breast cancer resistance protein (BCRP) function and expression using primary cultured rat brain microvessel endothelial cells (rBMECs) as an in vitro model of the blood brain barrier (BBB). The prazosin uptake assay and western blot analysis were used to assess the function and expression of BCRP, respectively. It was noted that the uptake of prazosin by rBMECs was time-, concentration-and temperature-dependent. The BCRP inhibitors novobiocin and imatinib mesylate significantly increased the uptake of prazosin by the cells in a concentration-dependent manner. The cells were also incubated with sera from diabetic rats for 72 h, serving as a diabetic in vitro model. We found that the uptake of prazosin by rBMECs incubated in the diabetic rat sera was 39.8% of that in normal rat sera, and insulin treatment reversed this decrease. Further results showed that insulin down-regulated the function and expression of BCRP in rBMECs in a concentration-dependent manner. Treatment with an antibody against the insulin receptor abolished the down-regulation of BCRP function and expression that was induced by insulin. These results indicate that insulin suppressed the function and expression of BCRPs in rBMEC primary cultures.
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影响因子：
11.4
作者：
Brendel, C.;Scharenberg, C.;Neubauer, A.
通讯作者：
Neubauer, A.
DOI：
10.1093/jnci/89.11.807
发表时间：
1997-06
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
U. Stein;W. Walther;C. Laurencot;G. Scheffer;R. Scheper;R. Shoemaker
通讯作者：
U. Stein;W. Walther;C. Laurencot;G. Scheffer;R. Scheper;R. Shoemaker
影响因子：
3.8
作者：
Cheol-Hee Choi;Kim Hs;Rha Hs;Jeong Jh;Park Yh;Min Yd;Kee Kh;Lim Dy
通讯作者：
Cheol-Hee Choi;Kim Hs;Rha Hs;Jeong Jh;Park Yh;Min Yd;Kee Kh;Lim Dy
影响因子：
11.2
作者：
Inger Brock;D. Hipfner;B. S. Nielsen;P. B. Jensen;R. Deeley;S. Cole;M. Sehested
通讯作者：
Inger Brock;D. Hipfner;B. S. Nielsen;P. B. Jensen;R. Deeley;S. Cole;M. Sehested
影响因子：
2.3
作者：
T. Emmel
通讯作者：
T. Emmel