@article{ref1,
title="Upregulation of autophagy decreases chlorine gas induced mitochondrial injury and lung inflammation",
journal="Free radical biology and medicine",
year="2015",
author="Jurkuvenaite, Asta and Benavides, Gloria A. and Komarova, Svetlana and Doran, Stephen F. and Johnson, Michelle and Aggarwal, Saurabh and Zhang, Jianhua and Darley-Usmar, Victor M. and Matalon, Sadis",
volume="85",
number="",
pages="83-94",
abstract="The mechanisms of toxicity during exposure of the airways to chlorinated biomolecules generated during the course of inflammation and chlorine (Cl2) gas are poorly understood. We hypothesized that lung epithelial cell mitochondria are damaged by Cl2 exposure and activation of autophagy mitigates this injury. To address this, NCI-H441 (Human lung adenocarcinoma epithelial) cells were exposed to Cl2 (100ppm/15min) and bioenergetics were assessed. One hour after Cl2, cellular bioenergetic function and mitochondrial membrane potential were decreased. These changes were associated with increased MitoSOX™ signal and treatment with the mitochondrial redox modulator, MitoQ, attenuated these bioenergetic defects. At six hours post exposure, there was significant increase of autophagy, which was associated with an improvement of mitochondrial function. Pre-treatment of H441 cells with trehalose (an autophagy activator) improved bioenergetic function whereas 3-methyladenine (an autophagy inhibitor) resulted in increased bioenergetic dysfunction 1h post Cl2 exposure. These data indicate that Cl2 induces bioenergetic dysfunction and autophagy plays a protective role in vitro. Addition of trehalose (2vol%) in the drinking water of C57BL/6 mice for 6 weeks, but not 1 week, before Cl2 (400ppm/30min) decreased white blood cells in the BAL at 6h post Cl2 by 70%. Acute administration of trehalose delivered through inhalation 24 and 1h prior to the exposure decreased alveolar permeability but not cell infiltration. These data indicate that Cl2 induces bioenergetic dysfunction associated with lung inflammation and suggests that autophagy plays a protective role.<p /> <p>Language: en</p>",
language="en",
issn="0891-5849",
doi="10.1016/j.freeradbiomed.2015.03.039",
url="http://dx.doi.org/10.1016/j.freeradbiomed.2015.03.039"
}