"4-Hydroxynonenal Regulates Mitochondrial Function in Human Small Airwa" by Lakshmi Galam, Athena Failla et al.
 

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.

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Creative Commons License
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

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