Inhibition of RPTOR Prevents Hyperoxia-induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice.

Inhibition of RPTOR Prevents Hyperoxia-induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice.
Am J Respir Cell Mol Biol. 2016 Jul 2;
Authors: Angara S, Syed M, Das P, Janér C, Pryhuber G, Rahman A, Andersson S, Homer RJ, Bhandari V
Abstract
Administration of supplemental oxygen remains a critical clinical intervention for survival of preterm infants with respiratory failure. However, prolonged exposure to hyperoxia can augment pulmonary damage, resulting in developmental lung diseases embodied as hyperoxia-induced acute lung injury (HALI) and bronchopulmonary dysplasia (BPD). We sought to investigate the role of autophagy in hyperoxia-induced apoptotic cell death in developing lungs. We identified increased autophagy signaling in hyperoxia exposed MLE-12 cells, freshly-isolated fetal Type II alveolar epithelial cells, lungs of newborn (NB) wild-type (WT) mice, and human NB with respiratory distress syndrome and evolving and established BPD. We found that hyperoxia exposure induces autophagy in a Trp53 dependent manner in MLE-12 cells and in neonatal mice lungs. Using pharmacological inhibitors and gene silencing techniques, we found that the activation of autophagy, upon hyperoxia exposure, demonstrated a protective role with an anti-apoptotic response. Specifically, inhibiting regulatory associated protein of MTOR, (RPTOR) in hyperoxia settings as evidenced by WT mice treated with Torin2 or administered...

Source: Am J Respir Cell Mol... - July 1, 2016 Category: Respiratory Medicine Authors: Angara S, Syed M, Das P, Janér C, Pryhuber G, Rahman A, Andersson S, Homer RJ, Bhandari V Tags: Am J Respir Cell Mol Biol Source Type: research