β-adrenergic receptor stimulation and adenoviral overexpression of superoxide dismutase prevent the hypoxia-mediated decrease in Na,K-ATPase and alveolar fluid reabsorption
β-adrenergic receptor stimulation and adenoviral overexpression of superoxide dismutase prevent the hypoxia-mediated decrease in Na,K-ATPase and alveolar fluid reabsorption
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DOI：
10.1074/jbc.m602064200
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发表时间：
2006-07-21
影响因子：
4.8
通讯作者：
Ridge, Karen M.
中科院分区：
文献类型：
--
作者：
Litvan, Juan;Briva, Arturo;Ridge, Karen M.
缺氧已被证明会导致肺水肿和损害肺水肿清除。本研究将大鼠离体肺暴露于pO（2）= 40 mm Hg 60 min或暴露于8% O-2 24 h，然后测定肺泡液体重吸收（AFR）和Na，K-ATP酶功能的变化。在离体和体内模型中，低氧水平严重损害AFR。低氧大鼠外周肺组织基底外侧膜Na，K-ATP酶活性和蛋白质丰度降低与AFR降低有关。β-肾上腺素能激动剂恢复了暴露于8%O-2的大鼠的AFR（从0.02 +/- 0.07 ml/h至0.59 +/- 0.03 ml/ h），这与基底外侧膜中Na，K-ATP酶蛋白丰度的平行增加有关。缺氧与活性氧的产生增加有关。因此，我们研究了是否过表达的SOD 2，锰超氧化物歧化酶，将防止缺氧介导的AFR减少。自主呼吸大鼠感染的复制缺陷型人5型腺病毒含有cDNA的SOD 2。将不含cDNA的其它相同病毒用作对照（Adnull）。低氧Adnull大鼠的AFR速率（0.12 ± 0.1 ml/ h）与低氧AdSOD 2和常氧对照大鼠（分别为0.47 ± 0.04 ml/ h和0.49 ± 0.02 ml/ h）相比有所降低，Na，K-ATP酶的变化平行。
Hypoxia has been shown to cause lung edema and impair lung edema clearance. In the present study, we exposed isolated rat lungs to pO(2) = 40 mm Hg for 60 min or rats to 8% O-2 for up to 24 h and then measured changes in alveolar fluid reabsorption (AFR) and Na, K-ATPase function. Low levels of oxygen severely impaired AFR in both ex vivo and in vivo models. The decrease in AFR was associated with a decrease in Na, K-ATPase activity and protein abundance in the basolateral membranes from peripheral lung tissue of hypoxic rats. beta-Adrenergic agonists restored AFR in rats exposed to 8% O-2 (from 0.02 +/- 0.07 ml/h to 0.59 +/- 0.03 ml/ h), which was associated with parallel increases in Na, K-ATPase protein abundance in the basolateral membrane. Hypoxia is associated with increased production of reactive oxygen species. Therefore, we examined whether overexpression of SOD2, manganese superoxide dismutase, would prevent the hypoxia-mediated decrease in AFR. Spontaneously breathing rats were infected with a replication-deficient human type 5 adenovirus containing cDNA for SOD2. An otherwise identical virus that contained no cDNA was used as a control (Adnull). Hypoxic Adnull rats had decreased rates of AFR (0.12 +/- 0.1 ml/ h) as compared with hypoxic AdSOD2 and normoxic control rats (0.47 +/- 0.04 ml/ h and 0.49 +/- 0.02 ml/ h, respectively), with parallel changes in Na, K- ATPase.