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Heme oxygenase-1 protects corexit 9500A-induced respiratory epithelial injury across species.

Li FJ, Duggal RN, Oliva OM, Karki S, Surolia R, Wang Z, Watson RD, Thannickal VJ, Powell M, Watts S, Kulkarni T, Batra H, Bolisetty S, Agarwal A, Antony VB - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

CE exposure induces dose-dependent increase of CRP.Following CE treatment for 4 hours, CRP expression in cells isolated from zebrafish was determined by qRT-PCR. CRP mRNA level is expressed as a ratio to control mRNA levels. Data are shown as mean ± SD of triplicate cultures and are from one experiment representative of three performed. ** p < 0.01 vs control by a one-way ANOVA with HSD test.
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pone.0122275.g006: CE exposure induces dose-dependent increase of CRP.Following CE treatment for 4 hours, CRP expression in cells isolated from zebrafish was determined by qRT-PCR. CRP mRNA level is expressed as a ratio to control mRNA levels. Data are shown as mean ± SD of triplicate cultures and are from one experiment representative of three performed. ** p < 0.01 vs control by a one-way ANOVA with HSD test.

Mentions: We further probed CRP in order to assess the inflammatory response mounted by CE exposed gills of zebrafish. CE concentrations as low as 5 ppm resulted in a 10.8 ±1.61 fold increase in CRP expression in zebrafish within 4 hours of exposure (Fig. 6). Expression levels increased by 16 ± 2.39 and 25 ± 4.5 fold when exposed to CE at concentrations of 10 ppm and 15 ppm, respectively. However, after 24 hours of exposure, no significant inductions of CRP were found (data not shown). These data suggest that CRP, as an acute phase reactant, may be involved in CE-induced apoptosis, probably via the CRP/ROS cascade.


Heme oxygenase-1 protects corexit 9500A-induced respiratory epithelial injury across species.

Li FJ, Duggal RN, Oliva OM, Karki S, Surolia R, Wang Z, Watson RD, Thannickal VJ, Powell M, Watts S, Kulkarni T, Batra H, Bolisetty S, Agarwal A, Antony VB - PLoS ONE (2015)

CE exposure induces dose-dependent increase of CRP.Following CE treatment for 4 hours, CRP expression in cells isolated from zebrafish was determined by qRT-PCR. CRP mRNA level is expressed as a ratio to control mRNA levels. Data are shown as mean ± SD of triplicate cultures and are from one experiment representative of three performed. ** p < 0.01 vs control by a one-way ANOVA with HSD test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383564&req=5

pone.0122275.g006: CE exposure induces dose-dependent increase of CRP.Following CE treatment for 4 hours, CRP expression in cells isolated from zebrafish was determined by qRT-PCR. CRP mRNA level is expressed as a ratio to control mRNA levels. Data are shown as mean ± SD of triplicate cultures and are from one experiment representative of three performed. ** p < 0.01 vs control by a one-way ANOVA with HSD test.
Mentions: We further probed CRP in order to assess the inflammatory response mounted by CE exposed gills of zebrafish. CE concentrations as low as 5 ppm resulted in a 10.8 ±1.61 fold increase in CRP expression in zebrafish within 4 hours of exposure (Fig. 6). Expression levels increased by 16 ± 2.39 and 25 ± 4.5 fold when exposed to CE at concentrations of 10 ppm and 15 ppm, respectively. However, after 24 hours of exposure, no significant inductions of CRP were found (data not shown). These data suggest that CRP, as an acute phase reactant, may be involved in CE-induced apoptosis, probably via the CRP/ROS cascade.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus