首页> 外文期刊>American Journal of Physiology >Rat renal glucose transporter SGLT1 exhibits zonal distribution and androgen-dependent gender differences.
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Rat renal glucose transporter SGLT1 exhibits zonal distribution and androgen-dependent gender differences.

机译:大鼠肾葡萄糖转运蛋白SGLT1表现出区域分布和雄激素依赖性性别差异。

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SGLT1 (SLC5A1) mediates a part of glucose and galactose reabsorption in the mammalian proximal tubule (PT), but the detailed localization of the transporter along the tubule is still disputable. Here, we used several methods to localize rat SGLT1 (rSGLT1) in the kidneys of intact and variously treated male (M) and female (F) rats. In immunoblots of isolated cortical (C) and outer stripe (OS) brush-border membranes (BBM), a peptide-specific polyclonal antibody for rSGLT1 labeled a sharp inzone-, and gender-dependent approximately 40-kDa protein and a broad approximately 75-kDa band that exhibited strong zonal (OS > C) and gender differences (F > M). In tissue cryosections, the antibody strongly stained BBM of the S3 PT segments in the OS and medullary rays (F > M) and smooth muscles of the blood vessels and renal capsule (F approximately M) and weakly stained the apical domain of other PT segments in the C (F approximately M). The phlorizin-sensitive uptake of d-[(3)H]galactose in BBM vesicles, as well as the tissue abundance of rSGLT1-specific mRNA, matched the immunoblotting data related to the 75-kDa protein and the immunostaining in S3, proving zonal and gender differences in the functional transporter. Ovariectomy had no effect, castration upregulated, whereas treatment of castrated rats with testosterone, but not with estradiol or progesterone, downregulated the 75-kDa protein and the immunostaining in S3. We conclude that in the rat kidney, the expression of SGLT1 is represented by a 75-kDa protein localized largely in the PT S3 segments, where it exhibits gender differences (F > M) at both the protein and mRNA levels that are caused by androgen inhibition.
机译:SGLT1(SLC5A1)在哺乳动物近端小管(PT)中介导了一部分葡萄糖和半乳糖的重吸收,但沿小管的转运蛋白的详细定位仍然存在争议。在这里,我们使用了几种方法来将大鼠SGLT1(rSGLT1)定位在完整的和经过不同处理的雄性(M)和雌性(F)大鼠的肾脏中。在分离的皮质(C)和外条纹(OS)刷状边界膜(BBM)的免疫印迹中,rSGLT1的肽特异性多克隆抗体标记了尖锐的区域依赖性和性别依赖性的约40kDa蛋白和约75kDa的宽泛蛋白-kDa带表现出强烈的纬向(OS> C)和性别差异(F> M)。在组织冰冻切片中,抗体对OS和髓质射线(F> M)以及血管和肾囊的平滑肌(F约M)的S3 PT节的BBM进行了强染色,而对其他PT节的顶端结构进行了弱染色在C(F约M)。 BBM囊泡中对苯丙氨酸敏感的d-[(3)H]半乳糖摄取以及rSGLT1特异性mRNA的组织丰度与75-kDa蛋白相关的免疫印迹数据和S3中的免疫染色相匹配,证明带状和功能性转运蛋白的性别差异。卵巢切除术没有作用,去势上调,而去势大鼠用睾丸激素而不是雌二醇或孕酮治疗下调了75 kDa蛋白和S3中的免疫染色。我们得出的结论是,在大鼠肾脏中,SGLT1的表达由一个主要位于PT S3区段中的75 kDa蛋白质代表,该蛋白质在由雄激素引起的蛋白质和mRNA水平上均表现出性别差异(F> M)抑制。

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