Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells
Oxidative stress is a main molecular mechanism that underlies cardiovascular diseases. A close relationship between reactive oxygen species (ROS) derived from NADPH oxidase (NOX) activity and the prostaglandin (PG) biosynthesis pathway has been described. However, little information is available abo...
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2020-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/637 |
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| author | Javier Marqués Adriana Cortés Álvaro Pejenaute Eduardo Ansorena Gloria Abizanda Felipe Prósper Juan José Martínez-Irujo Carlos de Miguel Guillermo Zalba |
| author_facet | Javier Marqués Adriana Cortés Álvaro Pejenaute Eduardo Ansorena Gloria Abizanda Felipe Prósper Juan José Martínez-Irujo Carlos de Miguel Guillermo Zalba |
| author_sort | Javier Marqués |
| collection | DOAJ |
| container_title | Cells |
| description | Oxidative stress is a main molecular mechanism that underlies cardiovascular diseases. A close relationship between reactive oxygen species (ROS) derived from NADPH oxidase (NOX) activity and the prostaglandin (PG) biosynthesis pathway has been described. However, little information is available about the interaction between NOX5 homolog-derived ROS and the PG pathway in the cardiovascular context. Our main goal was to characterize NOX5-derived ROS effects in PG homeostasis and their potential relevance in cardiovascular pathologies. For that purpose, two experimental systems were employed: an adenoviral NOX5-β overexpression model in immortalized human aortic endothelial cells (TeloHAEC) and a chronic infarction in vivo model developed from a conditional endothelial NOX5 knock-in mouse. NOX5 increased cyclooxygenase-2 isoform (COX-2) expression and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) production through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in TeloHAEC. Protein kinase C (PKC) activation and intracellular calcium level (Ca<sup>++</sup>) mobilization increased ROS production and NOX5 overexpression, which promoted a COX-2/PGE<sub>2</sub> response in vitro. In the chronic infarction model, mice encoding endothelial NOX5 enhanced the cardiac mRNA expression of COX-2 and PGES, suggesting a COX-2/PGE<sub>2</sub> response to NOX5 presence in an ischemic situation. Our data support that NOX5-derived ROS may modulate the COX-2/PGE<sub>2</sub> axis in endothelial cells, which might play a relevant role in the pathophysiology of heart infarction. |
| format | Article |
| id | doaj-art-5aa5bfcd9c2d4f489b769b4191c858ba |
| institution | Directory of Open Access Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-5aa5bfcd9c2d4f489b769b4191c858ba2025-08-19T21:23:50ZengMDPI AGCells2073-44092020-03-019363710.3390/cells9030637cells9030637Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial CellsJavier Marqués0Adriana Cortés1Álvaro Pejenaute2Eduardo Ansorena3Gloria Abizanda4Felipe Prósper5Juan José Martínez-Irujo6Carlos de Miguel7Guillermo Zalba8Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, SpainDepartment of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, SpainDepartment of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, SpainDepartment of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, SpainNavarra Institute for Health Research (IdiSNA), 31008 Pamplona, SpainNavarra Institute for Health Research (IdiSNA), 31008 Pamplona, SpainDepartment of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, SpainDepartment of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, SpainDepartment of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, SpainOxidative stress is a main molecular mechanism that underlies cardiovascular diseases. A close relationship between reactive oxygen species (ROS) derived from NADPH oxidase (NOX) activity and the prostaglandin (PG) biosynthesis pathway has been described. However, little information is available about the interaction between NOX5 homolog-derived ROS and the PG pathway in the cardiovascular context. Our main goal was to characterize NOX5-derived ROS effects in PG homeostasis and their potential relevance in cardiovascular pathologies. For that purpose, two experimental systems were employed: an adenoviral NOX5-β overexpression model in immortalized human aortic endothelial cells (TeloHAEC) and a chronic infarction in vivo model developed from a conditional endothelial NOX5 knock-in mouse. NOX5 increased cyclooxygenase-2 isoform (COX-2) expression and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) production through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in TeloHAEC. Protein kinase C (PKC) activation and intracellular calcium level (Ca<sup>++</sup>) mobilization increased ROS production and NOX5 overexpression, which promoted a COX-2/PGE<sub>2</sub> response in vitro. In the chronic infarction model, mice encoding endothelial NOX5 enhanced the cardiac mRNA expression of COX-2 and PGES, suggesting a COX-2/PGE<sub>2</sub> response to NOX5 presence in an ischemic situation. Our data support that NOX5-derived ROS may modulate the COX-2/PGE<sub>2</sub> axis in endothelial cells, which might play a relevant role in the pathophysiology of heart infarction.https://www.mdpi.com/2073-4409/9/3/637oxidative stressnadph oxidase 5cox-2pge<sub>2</sub>chronic infarctionpkcnf-κb |
| spellingShingle | Javier Marqués Adriana Cortés Álvaro Pejenaute Eduardo Ansorena Gloria Abizanda Felipe Prósper Juan José Martínez-Irujo Carlos de Miguel Guillermo Zalba Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells oxidative stress nadph oxidase 5 cox-2 pge<sub>2</sub> chronic infarction pkc nf-κb |
| title | Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells |
| title_full | Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells |
| title_fullStr | Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells |
| title_full_unstemmed | Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells |
| title_short | Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells |
| title_sort | induction of cyclooxygenase 2 by overexpression of the human nadph oxidase 5 nox5 gene in aortic endothelial cells |
| topic | oxidative stress nadph oxidase 5 cox-2 pge<sub>2</sub> chronic infarction pkc nf-κb |
| url | https://www.mdpi.com/2073-4409/9/3/637 |
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