Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier
Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier
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DOI：
10.1124/dmd.104.001024
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发表时间：
2005-01-01
影响因子：
3.9
通讯作者：
Cherrington, NJ
中科院分区：
文献类型：
--
作者：
Augustine, LM;Markelewicz, RJ;Cherrington, NJ
外源性和内源性转运蛋白的一个主要功能是将各种有机物质跨细胞膜移动。支持细胞通过形成生理屏障，限制暴露于潜在的毒性底物，或相反地，促进睾丸内外源性物质的摄取，在保护发育中的生殖细胞中发挥重要作用。本研究的目的是定量测定各种转运蛋白在成年SD大鼠分离的支持细胞中的组成型表达。通过分支DNA信号放大法在分离的Sertoli细胞中测量以下mRNA水平：多药耐药（Mdr）蛋白1a、1b和2;多药耐药蛋白（Mrp）1、2、3、4、5、6、7和8;牛磺胆酸钠共转运多肽;胆盐排泄蛋白;回肠胆汁酸转运蛋白; AbcG 5和AbcG 8;有机阴离子转运多肽（Oatp）1、2、3、4、5、9和12;前列腺素转运蛋白（Pgt）;睾丸特异性转运蛋白（Tst）1和Tst 2;有机阴离子转运蛋白（Oat）1、2、3和K;有机阳离子转运蛋白（Oct）1、2、3、N1和N2;二价金属转运蛋白（Dmt）1、Menke's和Wilson's;锌转运蛋白（Znt）1;平衡核苷转运蛋白（Ent）1和2;浓缩核苷转运蛋白（Cnt）1和2;以及肽转运蛋白（Pept）1和2。还测定了整个睾丸、肝脏、肾脏和回肠中的水平，以提供测定相对表达水平的参考。Mrp 8，Tst 1和2，Ent 1和2在支持细胞中的表达水平高于肝脏，肾脏或回肠，而Mrp 1，5和7，Mdr 2，Oatp 3，Oat 2，OctN 2，Dmt 1，Menke's，Wilson's和Znt 1都在支持细胞中显著表达，但支持细胞表达不是最高表达的组织。其余的转运蛋白在分离的支持细胞中以低水平表达。此外，Mrp 1，Mrp 7，Mrp 8，Tst 1，Tst 2，OctN 2，Wilson’s，Znt 1，Ent 1和Ent 2的表达水平在分离的支持细胞中高于整个睾丸。支持细胞中转运蛋白的组成型表达可以提供对可能由支持细胞转运的外源性物质的范围的深入了解，从而提供对血-睾丸屏障功能的机械理解。
A major function of xenobiotic and endobiotic transporters is to move a wide range of organic substances across cell membranes. Sertoli cells play an important role in protecting developing germ cells by forming a physiological barrier, limiting exposure to potentially toxic substrates, or conversely, facilitating uptake of xenobiotics within the testis. The aim of this study was to quantitatively determine the constitutive expression of various transporters in isolated Sertoli cells from adult Sprague-Dawley rats. The following mRNA levels were measured in isolated Sertoli cells by the branched DNA signal amplification method, multidrug resistance (Mdr) protein 1a, 1b, and 2; multiple drug resistance protein (Mrp) 1, 2, 3, 4, 5, 6, 7, and 8; sodium taurocholate cotransporting polypeptide; bile salt excretory protein; ileal bile acid transporter; AbcG5 and AbcG8; organic anion transporting polypeptide ( Oatp) 1, 2, 3, 4, 5, 9, and 12; prostaglandin transporter (Pgt); testis-specific transporter (Tst) 1 and Tst2; organic anion transporter ( Oat) 1, 2, 3, and K; organic cation transporter (Oct) 1, 2, 3, N1, and N2; divalent metal transporter (Dmt) 1, Menke's, and Wilson's; zinc transporter (Znt) 1; equilibrative nucleoside transporter (Ent) 1 and 2; concentrative nucleoside transporter (Cnt) 1 and 2; and peptide transporter (Pept) 1 and 2. Levels were also determined in whole testis, liver, kidney, and ileum to provide a reference for determining relative expression levels. Mrp8, Tst1 and 2, and Ent1 and 2 were expressed in Sertoli cells at higher levels than in liver, kidney, or ileum, whereas Mrp1, 5, and 7, Mdr2, Oatp3, Oat2, OctN2, Dmt1, Menke's, Wilson's, and Znt1 were all significantly expressed in Sertoli cells, but Sertoli cell expression was not the tissue of highest expression. The remaining transporters were expressed at low levels in isolated Sertoli cells. Additionally, expression levels of Mrp1, Mrp7, Mrp8, Tst1, Tst2, OctN2, Wilson's, Znt1, Ent1, and Ent2 were greater in isolated Sertoli cells than in whole testis. Constitutive expression of transporters in Sertoli cells may provide an insight into the range of xenobiotics that can potentially be transported by Sertoli cells and thereby provide a mechanistic understanding of blood-testis barrier function.