Activated Akt Protects the Lung from Oxidant-induced Injury and Delays Death of Mice

doi:10.1084/jem.193.4.545

Published online 20 February 2001.

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© The Rockefeller University Press, 0022-1007/2001/2/545/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 4, February 19, 2001 545-550

Brief Definitive Report

Activated Akt Protects the Lung from Oxidant-induced Injury and Delays Death of Mice

Yunbiao Lu^a, Lisa Parkyn^a, Leo E. Otterbein^a, Yasuko Kureishi^b, Kenneth Walsh^b, Anuradha Ray^a, and Prabir Ray^a
^a Department of Internal Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, New Haven, Connecticut 06520
^b Division of Cardiovascular Research, St. Elizabeth's Medical Center and Program in Cell, Molecular and Developmental Biology, Sackler School of Biomedical Studies, Tufts University School of Medicine, Boston, Massachusetts 02135

Correspondence to: Prabir Ray, Department of Internal Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, 333 Cedar St., LCI 105, New Haven, CT 06520. Tel:203-785-3620 Fax:203-785-3826 E-mail:prabir.ray{at}yale.edu.

Oxidant-induced injury to the lung causes extensive damage tolung epithelial cells. Impaired protection and repair of thelung epithelium can result in death. The serine-threonine kinaseAkt has been implicated in inhibiting cell death induced bydifferent stimuli including growth factor withdrawal, cell cyclediscordance, DNA damage, and loss of cell adhesion in differentcell types. However, the in vivo relevance of this prosurvivalpathway has not been explored. Here we show that a constitutivelyactive form of Akt introduced intratracheally into the lungsof mice by adenovirus gene transfer techniques protects micefrom hyperoxic pulmonary damage and delays death of mice. Thisis the first demonstration of the in vivo protective functionof Akt in the context of oxidant-induced lung injury.

Key Words: hyperoxia, lung, Akt, apoptosis, survival

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