Decreased expression of both the α1- and α2-subunits of the Na-K-ATPase reduces maximal alveolar epithelial fluid clearance
Decreased expression of both the α1- and α2-subunits of the Na-K-ATPase reduces maximal alveolar epithelial fluid clearance
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DOI：
10.1152/ajplung.00464.2004
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发表时间：
2005-07-01
影响因子：
4.9
通讯作者：
Matthay, MA
中科院分区：
文献类型：
--
作者：
Looney, MR;Sartori, C;Matthay, MA
鲁尼、马克·R.、克劳迪奥·萨托里、桑塔努·查克拉博蒂、保罗·f·詹姆斯、杰里·b·林格尔和迈克尔·a·马修。na - k - atp酶α(1)-亚基和α(2)-亚基的表达降低可减少肺泡上皮液的最大清除率。[J] .中国生物医学工程学报，2016,31(2):387 - 398。2005年3月18日首次出版；doi: 10.1152 / ajplung.00464.2004。-上皮钠通道功能受损容易导致肺水肿的延迟吸收和更严重的实验性肺损伤，而即使一小部分正常的na - k - atp酶活性也被认为足以维持正常的离子运输。然而，缺乏直接证据。因此，我们研究了na - k - atp酶α(1)-和/或α(2)-亚基肺蛋白表达降低50%的小鼠的基线和cAMP刺激肺泡液清除（AFC）。α(1)（+/-）或α(2)（+/-）小鼠的基础AFC和刺激AFC与野生型幼崽相比没有差异。复合杂合小鼠(α (1)(+/-)/ α(2)(+/-))基底AFC正常。然而，联合α (1)(+/-)/ α(2)（+/-）小鼠与野生型幼崽相比，camp刺激的AFC显著降低（11.1 +/- 1.0 vs. 14.9 +/- 1.8%/30 min, P < 0.001）。当暴露于96小时的> 95%高氧环境时，α(1)（+/-）或α(2)（+/-）小鼠受刺激AFC的减少与野生型窝鼠相比，与更多的肺水肿无关（肺干湿比分别为6.6 +/- 0.9和5.9 +/- 1.1,P =无统计学意义）。因此，na - k - atp酶α(1)-或α(2)-亚基蛋白表达减少50%不会损害基础或刺激AFC。然而，na - k - atp酶的α(1)-和α(2)-亚基的50%蛋白减少会产生次极大的AFC刺激，这表明α(1)-和α(2)-亚基在camp依赖性肺泡上皮液清除中具有协同作用。
Looney, Mark R., Claudio Sartori, Santanu Chakraborty, Paul F. James, Jerry B. Lingrel, and Michael A. Matthay. Decreased expression of both the alpha(1)- and alpha(2)- subunits of the Na-K-ATPase reduces maximal alveolar epithelial fluid clearance. Am J Physiol Lung Cell Mol Physiol 289: L104-L110, 2005. First published March 18, 2005; doi:10.1152/ajplung.00464.2004.-Impaired epithelial sodium channel function predisposes to delayed resorption of pulmonary edema and more severe experimental lung injury, whereas even a small fraction of the normal Na-K-ATPase activity is thought to be sufficient to maintain normal ion transport. However, direct proof is lacking. Therefore, we studied baseline and cAMP stimulated alveolar fluid clearance (AFC) in mice with a 50% decrease in lung protein expression of the alpha(1)- and/or alpha(2)-subunit of the Na-K-ATPase. There was no difference in basal and stimulated AFC in alpha(1)(+/-) or alpha(2)(+/-) mice compared with wild-type littermates. Also, the compound heterozygous mice (alpha(1)(+/-)/alpha(2)(+/-)) had normal basal AFC. However, the combined alpha(1)(+/-)/alpha(2)(+/-) mice showed a significant decrease in cAMP-stimulated AFC compared with wild-type littermates (11.1 +/- 1.0 vs. 14.9 +/- 1.8%/30 min, P < 0.001). When exposed to 96 h of > 95% hyperoxia, the decrease in stimulated AFC in the alpha(1)(+/-) or alpha(2)(+/-) mice was not associated with more lung edema compared with wild-type littermates ( lung wet-to-dry weight ratio 6.6 +/- 0.9 vs. 5.9 +/- 1.1, respectively; P = not significant). Thus a 50% decrease in protein expression of the alpha(1)- or alpha(2)- subunits of the Na-K-ATPase does not impair basal or stimulated AFC. However, a 50% protein reduction in both the alpha(1)- and alpha(2)- subunits of the Na-K-ATPase produces a submaximal stimulated AFC, suggesting a synergistic role for alpha(1)- and alpha(2)-subunits in cAMP-dependent alveolar epithelial fluid clearance.