Seminar - Cyclic Stretch Induced Oxidative Injury Increases Alveolar Permeability via ERK-NF-kB Signaling
Date: May 18, 2012
Time: 4:00 PM
Location: Papadakis Integrated Sciences Building, Room: 120
Nurit Davidovich, PhD
Department of Bioengineering
University of Pennsylvania
Mechanical ventilation with high tidal volumes has been associated with pulmonary alveolar flooding. Understanding the mechanisms underlying cyclic stretch-induced increases in alveolar epithelial permeability may be important in designingpreventive measures for acute lung injury. In this work, we sought to assess whether cyclic stretch leads to the generation of reactive oxygen species which, in turn, increase type I epithelial cell monolayer permeability via activation of nuclear factor-kappaB (NF-kB) and extracellular signal-regulated kinase (ERK). High levels of ROS and of superoxide and NO specifically were detected in cells stretched at 37 percent DSA for 10-120 minutes. Exogenous superoxide and NO stimulation each increased epithelial permeability in unstretched cells, which was preventable by the NF-kB inhibitor MG132. Cyclic stretch-induced increase in permeability was decreased by thesuperoxide scavenger Tiron and by MG132. Furthermore, cyclic stretch increased the activation of the NF-kB signaling pathway which was significantly decreasedwith U0126. Our data suggest that cyclic stretch induces oxidative stress, which mediates increases in alveolar epithelial monolayer permeability via NF-kB activation and ERK phosphorylation.
Dr. Davidovich is currently a postdoctoral researcher at the University of Pennsylvania, where her main research projects are focused on the investigation of the mechanisms underlying ventilator-induced lung injury. Specifically, she studies oxidative stress and EGF receptor response to cyclic stretch in primary rat alveolar epithelial cells. Her PhD research tested the effects of airflow-induced shear stresses on nasal epithelial cell function. She has gained valuable experience in small animal handling, isolation of primary cells and tissue slices, molecular biology techniques and microscopy, experimental protocol development and data analysis, finite element and numerical computational models, microfabrication, and design and fabrication of mechanical flow systems.
The Papadakis Integrated Sciences Building is located on the northeast corner of 33rd and Chestnut Streets.