PUBLICATION
Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species
- Authors
- Li, F.J., Duggal, R.N., Oliva, O.M., Karki, S., Surolia, R., Wang, Z., Watson, R.D., Thannickal, V.J., Powell, M., Watts, S., Kulkarni, T., Batra, H., Bolisetty, S., Agarwal, A., Antony, V.B.
- ID
- ZDB-PUB-150404-9
- Date
- 2015
- Source
- PLoS One 10: e0122275 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Actins/genetics
- Actins/metabolism
- Animals
- Apoptosis/drug effects
- Brachyura
- Bronchi/cytology
- Bronchi/drug effects*
- Bronchi/enzymology
- C-Reactive Protein/genetics
- C-Reactive Protein/metabolism
- Cadherins/genetics
- Cadherins/metabolism
- Caspase 3/genetics
- Caspase 3/metabolism
- Edema/chemically induced
- Edema/genetics*
- Edema/metabolism
- Edema/pathology
- Epithelial Cells/cytology
- Epithelial Cells/drug effects*
- Epithelial Cells/enzymology
- Focal Adhesion Kinase 1/genetics
- Focal Adhesion Kinase 1/metabolism
- Gene Expression Regulation
- Gills/drug effects
- Gills/enzymology
- Heme Oxygenase-1/genetics*
- Heme Oxygenase-1/metabolism
- Humans
- Lipids/toxicity*
- Mice
- Mice, Knockout
- NADPH Oxidases/genetics
- NADPH Oxidases/metabolism
- Occludin/genetics
- Occludin/metabolism
- Organometallic Compounds/pharmacology
- Permeability/drug effects
- Reactive Oxygen Species/metabolism
- Surface-Active Agents/toxicity*
- Zebrafish
- Zonula Occludens-1 Protein/genetics
- Zonula Occludens-1 Protein/metabolism
- Zonula Occludens-2 Protein/genetics
- Zonula Occludens-2 Protein/metabolism
- PubMed
- 25835394 Full text @ PLoS One
Citation
Li, F.J., Duggal, R.N., Oliva, O.M., Karki, S., Surolia, R., Wang, Z., Watson, R.D., Thannickal, V.J., Powell, M., Watts, S., Kulkarni, T., Batra, H., Bolisetty, S., Agarwal, A., Antony, V.B. (2015) Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species. PLoS One. 10:e0122275.
Abstract
The effects of Corexit 9500A (CE) on respiratory epithelial surfaces of terrestrial mammals and marine animals are largely unknown. This study investigated the role of CE-induced heme oxygenase-1 (HO-1), a cytoprotective enzyme with anti-apoptotic and antioxidant activity, in human bronchial airway epithelium and the gills of exposed aquatic animals. We evaluated CE-mediated alterations in human airway epithelial cells, mice lungs and gills from zebrafish and blue crabs. Our results demonstrated that CE induced an increase in gill epithelial edema and human epithelial monolayer permeability, suggesting an acute injury caused by CE exposure. CE induced the expression of HO-1 as well as C-reactive protein (CRP) and NADPH oxidase 4 (NOX4), which are associated with ROS production. Importantly, CE induced caspase-3 activation and subsequent apoptosis of epithelial cells. The expression of the intercellular junctional proteins, such as tight junction proteins occludin, zonula occludens (ZO-1), ZO-2 and adherens junctional proteins E-cadherin and Focal Adhesion Kinase (FAK), were remarkably inhibited by CE, suggesting that these proteins are involved in CE-induced increased permeability and subsequent apoptosis. The cytoskeletal protein F-actin was also disrupted by CE. Treatment with carbon monoxide releasing molecule-2 (CORM-2) significantly inhibited CE-induced ROS production, while the addition of HO-1 inhibitor, significantly increased CE-induced ROS production and apoptosis, suggesting a protective role of HO-1 or its reaction product, CO, in CE-induced apoptosis. Using HO-1 knockout mice, we further demonstrated that HO-1 protected against CE-induced inflammation and cellular apoptosis and corrected CE-mediated inhibition of E-cadherin and FAK. These observations suggest that CE activates CRP and NOX4-mediated ROS production, alters permeability by inhibition of junctional proteins, and leads to caspase-3 dependent apoptosis of epithelial cells, while HO-1 and its reaction products protect against oxidative stress and apoptosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping