Salt-inducible kinase 1 is present in lung alveolar epithelial cells and regulates active sodium transport.
Salt-inducible kinase 1 is present in lung alveolar epithelial cells and regulates active sodium transport.
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DOI：
10.1016/j.bbrc.2011.04.100
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发表时间：
2011-05-27
影响因子：
3.1
通讯作者：
Bertorello, Alejandro M.
中科院分区：
文献类型：
--
作者：
Eneling, Kristina;Chen, Jiwang;Welch, Lynn C.;Takemori, Hiroshi;Sznajder, Jacob I.;Bertorello, Alejandro M.
上皮细胞中的盐诱导蛋白1(SIK1)介导了主动钠转运(Na+，K+-ATPase介导)的增加，以响应细胞内钠浓度的升高。在肺泡上皮细胞中，β-肾上腺素能刺激增加主动钠转运，增加肺水肿清除。因此，我们试图确定SIK1是否存在于肺上皮细胞中，并检测异丙肾上腺素依赖的Na+，K+-ATPase刺激是否通过SIK1活性介导。三种sik亚型均存在于呼吸道上皮细胞、大鼠和小鼠肺的肺泡上皮细胞1型和2型，以及代表肺泡上皮的人和小鼠细胞系中。在小鼠肺上皮细胞中，SIK1与Na+，K+-ATPaseα-亚基相关，异丙肾上腺素增加SIK1的活性。异丙肾上腺素可增加Na+，K+-ATPase活性和质膜上Na+，K+-ATPase分子的掺入。此外，这些效应在使用shRNA缺失SIK1的细胞中被取消，或者在过度表达SIK1激酶缺失突变体的细胞中被取消。这些结果证明SIK1存在于肺上皮细胞中，其功能与异丙肾上腺素调节主动钠转运的作用有关。因此，SIK1可能成为旨在改善肺水肿清除的药物发现的重要靶点。
Salt-inducible kinase 1 (SIK1) in epithelial cells mediates the increases in active sodium transport (Na+,K+-ATPase-mediated) in response to elevations in the intracellular concentration of sodium. In lung alveolar epithelial cells increases in active sodium transport in response to β-adrenergic stimulation increases pulmonary edema clearance. Therefore, we sought to determine whether SIK1 is present in lung epithelial cells and to examine whether isoproterenol-dependent stimulation of Na+,K+-ATPase is mediated via SIK1 activity. All three SIK isoforms were present in airway epithelial cells, and in alveolar epithelial cells type 1 and type 2 from rat and mouse lungs, as well as from human and mouse cell lines representative of lung alveolar epithelium. In mouse lung epithelial cells, SIK1 associated with the Na+,K+-ATPase α-subunit, and isoproterenol increased SIK1 activity. Isoproterenol increased Na+,K+-ATPase activity and the incorporation of Na+,K+-ATPase molecules at the plasma membrane. Furthermore, those effects were abolished in cells depleted of SIK1 using shRNA, or in cells overexpressing a SIK1 kinase-deficient mutant. These results provide evidence that SIK1 is present in lung epithelial cells and that its function is relevant for the action of isoproterenol during regulation of active sodium transport. As such, SIK1 may constitute an important target for drug discovery aimed at improving the clearance of pulmonary edema.
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影响因子：
3.9
作者：
Blanco, G;Sánchez, G;Mercer, RW
通讯作者：
Mercer, RW
DOI：
10.1165/rcmb.2008-0365oc
发表时间：
2009-12-01
影响因子：
6.4
作者：
Lecuona, Emilia;Sun, Haiying;Sznajder, Jacob I.
通讯作者：
Sznajder, Jacob I.
DOI：
10.1152/ajplung.1999.276.6.l1046
发表时间：
1999-06-01
影响因子：
4.9
作者：
Jain, L;Chen, XJ;Eaton, DC
通讯作者：
Eaton, DC
影响因子：
5
作者：
Chen, JW;Chen, ZM;Liu, L
通讯作者：
Liu, L
影响因子：
4.8
作者：
Litvan, Juan;Briva, Arturo;Ridge, Karen M.
通讯作者：
Ridge, Karen M.