Activated Akt protects the lung from oxidant-induced injury and delays death of mice.
Oxidant-induced injury to the lung causes extensive damage to lung epithelial cells. Impaired protection and repair of the lung epithelium can result in death. The serine-threonine kinase Akt has been implicated in inhibiting cell death induced by different stimuli including growth factor withdrawal, cell cycle discordance, DNA damage, and loss of cell adhesion in different cell types. However, the in vivo relevance of this prosurvival pathway has not been explored. Here we show that a constitutively active form of Akt introduced intratracheally into the lungs of mice by adenovirus gene transfer techniques protects mice from hyperoxic pulmonary damage and delays death of mice. This is the first demonstration of the in vivo protective function of Akt in the context of oxidant-induced lung injury.
Lu
Y
Y
Department of Internal Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Parkyn
L
L
Otterbein
L E
LE
Kureishi
Y
Y
Walsh
K
K
Ray
A
A
Ray
P
P
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006801:Humans; D018496:Hyperoxia / Q000401:mortality*; D008168:Lung / Q000187:drug effects*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D016877:Oxidants / Q000009:adverse effects*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors / Q000378:metabolism; D051025:bcl-Associated Death Protein
C494819:BAD protein, human; C494820:Bad protein, mouse; D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D016877:Oxidants; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051025:bcl-Associated Death Protein; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt