Document Type
Article
Publication Date
2015
Keywords
acute lung injury, hyperoxia, ROS, 4-HNE, mitochondrial dysfunction, Immunology and Microbiology Section, Immune response, Immunity
Digital Object Identifier (DOI)
https://doi.org/10.18632/oncotarget.6131
Abstract
Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response.
Rights Information
This work is licensed under a Creative Commons Attribution 3.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Oncotarget, v. 6, p. 41508-41521
Scholar Commons Citation
Galam, Lakshmi; Failla, Athena; Soundararajan, Ramani; Lockey, Richard F.; and Kolliputi, Narasaiah, "4-Hydroxynonenal Regulates Mitochondrial Function in Human Small Airway Epithelial Cells" (2015). Internal Medicine Faculty Publications. 140.
https://digitalcommons.usf.edu/intmed_facpub/140
