Cargando…
Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383564/ https://www.ncbi.nlm.nih.gov/pubmed/25835394 http://dx.doi.org/10.1371/journal.pone.0122275 |
_version_ | 1782364763183906816 |
---|---|
author | Li, Fu Jun Duggal, Ryan N. Oliva, Octavio M. Karki, Suman Surolia, Ranu Wang, Zheng Watson, R. Douglas Thannickal, Victor J. Powell, Mickie Watts, Stephen Kulkarni, Tejaswini Batra, Hitesh Bolisetty, Subhashini Agarwal, Anupam Antony, Veena B. |
author_facet | Li, Fu Jun Duggal, Ryan N. Oliva, Octavio M. Karki, Suman Surolia, Ranu Wang, Zheng Watson, R. Douglas Thannickal, Victor J. Powell, Mickie Watts, Stephen Kulkarni, Tejaswini Batra, Hitesh Bolisetty, Subhashini Agarwal, Anupam Antony, Veena B. |
author_sort | Li, Fu Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4383564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43835642015-04-09 Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species Li, Fu Jun Duggal, Ryan N. Oliva, Octavio M. Karki, Suman Surolia, Ranu Wang, Zheng Watson, R. Douglas Thannickal, Victor J. Powell, Mickie Watts, Stephen Kulkarni, Tejaswini Batra, Hitesh Bolisetty, Subhashini Agarwal, Anupam Antony, Veena B. PLoS One Research Article 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. Public Library of Science 2015-04-02 /pmc/articles/PMC4383564/ /pubmed/25835394 http://dx.doi.org/10.1371/journal.pone.0122275 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Li, Fu Jun Duggal, Ryan N. Oliva, Octavio M. Karki, Suman Surolia, Ranu Wang, Zheng Watson, R. Douglas Thannickal, Victor J. Powell, Mickie Watts, Stephen Kulkarni, Tejaswini Batra, Hitesh Bolisetty, Subhashini Agarwal, Anupam Antony, Veena B. Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species |
title | Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species |
title_full | Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species |
title_fullStr | Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species |
title_full_unstemmed | Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species |
title_short | Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species |
title_sort | heme oxygenase-1 protects corexit 9500a-induced respiratory epithelial injury across species |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383564/ https://www.ncbi.nlm.nih.gov/pubmed/25835394 http://dx.doi.org/10.1371/journal.pone.0122275 |
work_keys_str_mv | AT lifujun hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT duggalryann hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT olivaoctaviom hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT karkisuman hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT suroliaranu hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT wangzheng hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT watsonrdouglas hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT thannickalvictorj hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT powellmickie hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT wattsstephen hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT kulkarnitejaswini hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT batrahitesh hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT bolisettysubhashini hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT agarwalanupam hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies AT antonyveenab hemeoxygenase1protectscorexit9500ainducedrespiratoryepithelialinjuryacrossspecies |