Extracellular glutathione peroxidase (Gpx3) binds specifically to basement membranes of mouse renal cortex tubule cells

Extracellular glutathione peroxidase (Gpx3) binds specifically to basement membranes of mouse renal cortex tubule cells
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DOI:
10.1152/ajprenal.00662.2009
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发表时间:
2010-05-01
影响因子:
4.2
通讯作者:
Burk, Raymond F.
Burk, Raymond F.
中科院分区:
医学2区
文献类型:
--
作者:
Olson, Gary E.;Whitin, John C.;Burk, Raymond F.

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奥尔森·葛,Whitin JC,Hill Ke,温弗瑞副总裁,Motley AK,Austin LM,Deal J,Cohen HJ,Burk RF。细胞外谷胱甘肽过氧化物酶(Gpx3)与小鼠肾皮质小管细胞基底膜特异性结合。Am J Physiol Renal Physiol 298:F1244-F1253,2010。首次发表于2009年12月16日;doi:10.1152/ajprenal.00662.2009。-谷胱甘肽过氧化物酶-3(Gpx3),也称为血浆或细胞外谷胱甘肽过氧化物酶,是一种主要由肾脏近端曲管细胞分泌的硒蛋白。在这项研究中,已经产生了Gpx3(-/-)小鼠,并发展了免疫细胞化学技术来研究Gpx3代谢。Gpx3(-/-)小鼠与Gpx3(-/-)小鼠保持相同的全身硒含量和尿硒排泄量。他们能耐受硒缺乏,没有明显的不良反应。Gpx3和硒蛋白P的同时敲除表明,这两种硒蛋白占血浆硒的97%。免疫细胞化学实验表明,Gpx3在体内和体外都选择性地与肾皮质近曲小管和远曲小管的基底膜结合。根据硒含量的计算,Gpx3的肾池是血浆池的两倍多。这些数据表明,Gpx3不参与调节硒的代谢。大量Gpx3与肾皮质基底膜的特异性结合强烈表明,肾皮质管周间隙需要谷胱甘肽过氧化物酶活性。
Olson GE, Whitin JC, Hill KE, Winfrey VP, Motley AK, Austin LM, Deal J, Cohen HJ, Burk RF. Extracellular glutathione peroxidase (Gpx3) binds specifically to basement membranes of mouse renal cortex tubule cells. Am J Physiol Renal Physiol 298: F1244-F1253, 2010. First published December 16, 2009; doi:10.1152/ajprenal.00662.2009.-Glutathione peroxidase-3 (Gpx3), also known as plasma or extracellular glutathione peroxidase, is a selenoprotein secreted primarily by kidney proximal convoluted tubule cells. In this study Gpx3(-/-) mice have been produced and immunocytochemical techniques have been developed to investigate Gpx3 metabolism. Gpx3(-/-) mice maintained the same whole-body content and urinary excretion of selenium as did Gpx3(-/-) mice. They tolerated selenium deficiency without observable ill effects. The simultaneous knockout of Gpx3 and selenoprotein P revealed that these two selenoproteins account for > 97% of plasma selenium. Immunocytochemistry experiments demonstrated that Gpx3 binds selectively, both in vivo and in vitro, to basement membranes of renal cortical proximal and distal convoluted tubules. Based on calculations using selenium content, the kidney pool of Gpx3 is over twice as large as the plasma pool. These data indicate that Gpx3 does not serve in the regulation of selenium metabolism. The specific binding of a large pool of Gpx3 to basement membranes in the kidney cortex strongly suggests a need for glutathione peroxidase activity in the cortical peritubular space.