Zhang R, Alper S L, Thorens B, Verkman A S
Department of Medicine, University of California, San Francisco 94143-0532.
J Clin Invest. 1991 Nov;88(5):1553-8. doi: 10.1172/JCI115466.
It has been proposed that the mercurial-sensitive water transporter in mammalian erythrocytes is the anion exchanger band 3 (AE1) and/or the glucose transporter, band 4.5 (GLUT1). Using a functional assay for water channel expression in Xenopus oocytes (Zhang, R., K. A. Logee, and A. S. Verkman. 1990. J. Biol. Chem. 265:15375-15378), we compared osmotic water permeability (Pf) of oocytes injected with water, reticulocyte mRNA, AE1 mRNA, and GLUT1 mRNA. Injection of oocytes with 5-50 ng of in vitro-transcribed AE1 mRNA had no effect on Pf, but increased trans-stimulated 36Cl uptake greater than fourfold in a dinitro-disulfonic stilbene (DNDS)-inhibitable manner. Injection with 1-50 ng of in vitro-transcribed GLUT1 mRNA increased 3H-methylglucose uptake greater than 15-fold in a cytochalasin B-sensitive manner and increased Pf from (3.7 +/- 0.4) x 10(-4) cm/s (SE, n = 16, 10 degrees C) in water-injected oocytes up to (13 +/- 1) x 10(-4) cm/s (n = 18). Both the increments in sugar and water transport were inhibited by cytochalasin B (25 microM) and phloretin (0.2 mM); neither was inhibited by 0.3 mM HgCl2. In oocytes injected with 50 ng of rabbit reticulocyte mRNA, the Pf of (18 +/- 2) x 10(-4) cm/s (n = 18) was reduced to (4.0 +/- 0.6) x 10(-4) cm/s (n = 10) by HgCl2, but was not inhibited by DNDS (0.4 mM), cytochalasin B or phloretin. Coinjection of reticulocyte mRNA with antisense oligodeoxyribonucleotides against AE1 or GLUT1 did not affect Pf, but inhibited completely the incremental uptake of 36Cl or 3H-methylglucose, respectively. Expression of size-fractionated mRNA from reticulocyte gave a 2-2.5-kb size for water channel mRNA, less than the 4-4.5-kb size for the Cl transporter. These results provide evidence that facilitated water transport in erythrocytes is mediated not by bands 3 or 4.5, but by distinct water transport protein(s).
有人提出,哺乳动物红细胞中对汞敏感的水转运体是阴离子交换蛋白带3(AE1)和/或葡萄糖转运体带4.5(GLUT1)。我们使用非洲爪蟾卵母细胞中水通道表达的功能测定法(Zhang, R., K. A. Logee, and A. S. Verkman. 1990. J. Biol. Chem. 265:15375 - 15378),比较了注射水、网织红细胞mRNA、AE1 mRNA和GLUT1 mRNA的卵母细胞的渗透水通透性(Pf)。向卵母细胞注射5 - 50 ng体外转录的AE1 mRNA对Pf没有影响,但以二硝基二磺酰基芪(DNDS)可抑制的方式使跨刺激的36Cl摄取增加了四倍以上。注射1 - 50 ng体外转录的GLUT1 mRNA以细胞松弛素B敏感的方式使3H - 甲基葡萄糖摄取增加了15倍以上,并使注射水的卵母细胞的Pf从(3.7±0.4)×10^(-4) cm/s(标准误,n = 16,10℃)增加到(13±1)×10^(-4) cm/s(n = 18)。糖和水转运的增加均受到细胞松弛素B(25 μM)和根皮素(0.2 mM)的抑制;两者均不受0.3 mM HgCl2的抑制。在注射50 ng兔网织红细胞mRNA的卵母细胞中,Pf为(18±2)×10^(-4) cm/s(n = 18),HgCl2使其降至(4.0±0.6)×10^(-4) cm/s(n = 10),但不受DNDS(0.4 mM)、细胞松弛素B或根皮素的抑制。将网织红细胞mRNA与针对AE1或GLUT1的反义寡脱氧核糖核苷酸共注射不影响Pf,但分别完全抑制了36Cl或3H - 甲基葡萄糖的增量摄取。对网织红细胞中大小分级的mRNA的表达分析表明,水通道mRNA的大小为2 - 2.5 kb,小于Cl转运体的4 - 4.5 kb。这些结果提供了证据,表明红细胞中易化水转运不是由带3或带4.5介导的,而是由不同的水转运蛋白介导的。