Tissue-specific damage in expression and function of breast cancer resistance protein in streptozotocin-induced diabetic rats
Tissue-specific damage in expression and function of breast cancer resistance protein in streptozotocin-induced diabetic rats
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发表时间：
2011
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通讯作者：
L. Xiao-dong
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作者：
L. Xiao-dong
本研究的目的是研究糖尿病是否会改变乳腺癌耐药蛋白（BCRP）在大脑皮层、海马、肝脏、采用Caco-2和HepG-2细胞系检测糖尿病大鼠血清中BCRP的表达和功能，并探讨胰岛素治疗是否能逆转糖尿病引起的BCRP表达和功能的改变。采用真实的时间定量聚合酶链反应（QT-PCR）和蛋白质印迹法（Western blot）检测糖尿病大鼠各组织中ATP结合盒转运体G2（ABCG 2）/BCRP mRNA和蛋白质的表达水平。定量聚合酶链反应（QT-PCR）分析显示，ABCG 2 mRNA在大脑皮层、肝脏和肠粘膜中的表达明显降低，在糖尿病5周和8周大鼠海马和肾脏中BCRP表达显著增加，Western blot结果与大多数组织中ABCG 2 mRNA表达的变化相一致，摄取实验结果表明，高胰岛素和高糖可能导致Caco-2细胞BCRP表达下调。结果表明，糖尿病对ABCG 2/BCRP表达和功能的损害具有组织特异性，在大鼠肝和肠黏膜中，高糖可能是导致BCRP改变的主要原因。
The purpose of the study was to investigate whether diabetes mellitus would alter breast cancer resistance protein(BCRP) expression and function in the cerebral cortex,hippocampus,liver,intestinal mucosa and kidney of rat and whether insulin treatment would reverse the alteration caused by diabetes.Abnormal factors in diabetic blood serum altering the expression and function of BCRP were investigated using Caco-2 and HepG-2 cells.Diabetic rats were induced by an intraperitoneal administration of 55 mg/kg of streptozotocin.ATP-binding cassette transporter G2(ABCG2)/BCRP mRNA and protein expression levels in the indicated tissues were evaluated by quantitative real time polymerase chain reaction(QT-PCR) analysis and Western blot,respectively.BCRP functional activities were estimated by the uptake of prazosin in Caco-2 and HepG-2 cells.QT-PCR analysis revealed that ABCG2 mRNA levels were significantly decreased in cerebral cortex,liver and intestinal mucosa,but were dramatically increased in hippocampus and kidney of 5-and 8-week diabetic rats.Western blot results were in accordance with the alterations of ABCG2 mRNA levels in most tissues.Uptake assay results demonstrated that high insulin and high glucose may cause the down-regulation of BCRP in Caco-2 and HepG-2 cells.The results demonstrated that diabetes damaged the ABCG2/BCRP expression and function in a tissue-specific manner;and in rat liver and intestinal mucosa,the alteration of BCRP under diabetic condition may be caused by high glucose level.