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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-4
pubmed:abstractText
Hypercapnia (elevated CO(2) levels) occurs as a consequence of poor alveolar ventilation and impairs alveolar fluid reabsorption (AFR) by promoting Na,K-ATPase endocytosis. We studied the mechanisms regulating CO(2)-induced Na,K-ATPase endocytosis in alveolar epithelial cells (AECs) and alveolar epithelial dysfunction in rats. Elevated CO(2) levels caused a rapid activation of AMP-activated protein kinase (AMPK) in AECs, a key regulator of metabolic homeostasis. Activation of AMPK was mediated by a CO(2)-triggered increase in intracellular Ca(2+) concentration and Ca(2+)/calmodulin-dependent kinase kinase-beta (CaMKK-beta). Chelating intracellular Ca(2+) or abrogating CaMKK-beta function by gene silencing or chemical inhibition prevented the CO(2)-induced AMPK activation in AECs. Activation of AMPK or overexpression of constitutively active AMPK was sufficient to activate PKC-zeta and promote Na,K-ATPase endocytosis. Inhibition or downregulation of AMPK via adenoviral delivery of dominant-negative AMPK-alpha(1) prevented CO(2)-induced Na,K-ATPase endocytosis. The hypercapnia effects were independent of intracellular ROS. Exposure of rats to hypercapnia for up to 7 days caused a sustained decrease in AFR. Pretreatment with a beta-adrenergic agonist, isoproterenol, or a cAMP analog ameliorated the hypercapnia-induced impairment of AFR. Accordingly, we provide evidence that elevated CO(2) levels are sensed by AECs and that AMPK mediates CO(2)-induced Na,K-ATPase endocytosis and alveolar epithelial dysfunction, which can be prevented with beta-adrenergic agonists and cAMP.
pubmed:grant
pubmed:commentsCorrections
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-11713096, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-11867640, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-11889333, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-11950946, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12087129, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12097271, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12107173, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12163513, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12372821, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12388081, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12519745, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12546677, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12600893, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12671055, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12818238, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-12972572, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-1382419, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-14511394, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-14614828, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-14976552, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15241090, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15477499, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15525685, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15528240, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15695495, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15905164, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15919715, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-15980064, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16014898, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16046906, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16054095, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16054096, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16141266, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16222038, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16234332, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16332922, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16356723, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16371601, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16614303, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16636055, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16644800, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16651523, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16809515, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16818670, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16844684, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-16880506, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17030366, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17045514, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17065225, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17147517, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17351061, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17525842, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17530222, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17550967, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-17690328, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-18043745, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-7744080, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-8887592, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-8910387, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-9535860, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-9759505, http://linkedlifedata.com/resource/pubmed/commentcorrection/18188452-9769335
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
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