Nadph oxidase regulates alveolar epithelial sodium channel activity and lung fluid balance in vivo via O2- signaling
Nadph oxidase regulates alveolar epithelial sodium channel activity and lung fluid balance in vivo via O2- signaling
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DOI：
10.1152/ajplung.00260.2011
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发表时间：
2012-02-01
影响因子：
4.9
通讯作者：
Helms, My N.
中科院分区：
文献类型：
--
作者：
Goodson, Preston;Kumar, Amrita;Helms, My N.
Goodson P, Kumar A, Jain L, Kundu K, Murthy N, Koval M, Helms MN。Nadph氧化酶通过O-2（-）信号调节肺泡上皮钠通道活性和肺液平衡。[J] .中国生物医学工程学报，2016,31(4):444 - 444。首次发表于2011年12月9日；doi: 10.1152 / ajplung.00260.2011。为了确定活性氧（ROS）和上皮钠通道（ENaC）在维持体内肺液平衡中的作用，我们使用了两种新的全动物成像方法。实时x线透视法定量气管内注入生理盐水后C57BL/6J小鼠肺内空气空间液含量；采用常规肺干湿重量比和埃文斯蓝作为肺水肿的测量，证实了结果。通过IT滴注氧化还原敏感染料hydro-Cy7，对小鼠肺中产生的ROS进行可视化和量化。我们发现，用Rac-1抑制剂NSC23766抑制NADPH氧化酶会导致肺泡泛洪，这与体内肺部ROS生成的减少有关。与Nox2在肺泡液体平衡中的作用一致，与野生型对照相比，Nox2（-/-）小鼠表现出增加的空气空间液体潴留。有趣的是，对C57BL/6J肺IT灌注LPS的透视分析显示，体内肺液清除和ROS生成的急性刺激被ROS清除剂tetramethylpiperidine- N-oxyl （TEMPO）消除。LPS的急性应用增加了大鼠1型细胞20个非选择性ENaC通道的活性；平均通道数和单通道打开概率（NPo）由0.14 +/- 0.04增加到0.62 +/- 0.23。将TEMPO应用于同一细胞贴附记录，ENaC NPo立即显著降低至0.04 +/- 0.03。这些数据表明，在体内，ROS具有通过增加ENaC活性来刺激肺液清除的能力。
Goodson P, Kumar A, Jain L, Kundu K, Murthy N, Koval M, Helms MN. Nadph oxidase regulates alveolar epithelial sodium channel activity and lung fluid balance in vivo via O-2(-) signaling. Am J Physiol Lung Cell Mol Physiol 302: L410-L419, 2012. First published December 9, 2011; doi:10.1152/ajplung.00260.2011.-To define roles for reactive oxygen species (ROS) and epithelial sodium channel (ENaC) in maintaining lung fluid balance in vivo, we used two novel whole animal imaging approaches. Live X-ray fluoroscopy enabled quantification of air space fluid content of C57BL/6J mouse lungs challenged by intratracheal (IT) instillation of saline; results were confirmed by using conventional lung wet-to-dry weight ratios and Evans blue as measures of pulmonary edema. Visualization and quantification of ROS produced in lungs was performed in mice that had been administered a redox-sensitive dye, hydro-Cy7, by IT instillation. We found that inhibition of NADPH oxidase with a Rac-1 inhibitor, NSC23766, resulted in alveolar flooding, which correlated with a decrease in lung ROS production in vivo. Consistent with a role for Nox2 in alveolar fluid balance, Nox2(-/-) mice showed increased retention of air space fluid compared with wild-type controls. Interestingly, fluoroscopic analysis of C57BL/6J lungs IT instilled with LPS showed an acute stimulation of lung fluid clearance and ROS production in vivo that was abrogated by the ROS scavenger tetramethylpiperidine- N-oxyl (TEMPO). Acute application of LPS increased the activity of 20 pS nonselective ENaC channels in rat type 1 cells; the average number of channel and single-channel open probability (NPo) increased from 0.14 +/- 0.04 to 0.62 +/- 0.23. Application of TEMPO to the same cell-attached recording caused an immediate significant decrease in ENaC NPo to 0.04 +/- 0.03. These data demonstrate that, in vivo, ROS has the capacity to stimulate lung fluid clearance by increasing ENaC activity.