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Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia

Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vasc...

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Autores principales: Mathias, Maxwell, Taylor, Joann, Mendralla, Elizabeth, Perez, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388997/
https://www.ncbi.nlm.nih.gov/pubmed/34439484
http://dx.doi.org/10.3390/antiox10081236
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author Mathias, Maxwell
Taylor, Joann
Mendralla, Elizabeth
Perez, Marta
author_facet Mathias, Maxwell
Taylor, Joann
Mendralla, Elizabeth
Perez, Marta
author_sort Mathias, Maxwell
collection PubMed
description Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor (VEGF) and nitric oxide (NO) signaling in vascular endothelium. We utilized a mouse model of neonatal hyperoxic lung injury and SOD3 knockout (KO) mice to evaluate its function during chronic hyperoxia exposure. Wild-type age-matched neonatal C57Bl/6 (WT) and SOD3(−/−) (KO) mice were placed in normoxia (21% FiO(2), RA) or chronic hyperoxia (75% FiO(2), O(2)) within 24 h of birth for 14 days continuously and then euthanized. Lungs were harvested for histologic evaluation, as well as comparison of antioxidant enzyme expression, SOD activity, VEGF expression, and portions of the NO signaling pathway. Surprisingly, KO-O(2) mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O(2) mice. KO-O(2) mice had increased total SOD activity and increased VEGF expression when compared to WT-O(2) mice. No genotype differences were noted in intracellular antioxidant enzyme expression or the NO signaling pathway. These results demonstrate that SOD3 KO mice can survive prolonged hyperoxia without exacerbation of alveolar or vascular phenotype.
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spelling pubmed-83889972021-08-27 Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia Mathias, Maxwell Taylor, Joann Mendralla, Elizabeth Perez, Marta Antioxidants (Basel) Article Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor (VEGF) and nitric oxide (NO) signaling in vascular endothelium. We utilized a mouse model of neonatal hyperoxic lung injury and SOD3 knockout (KO) mice to evaluate its function during chronic hyperoxia exposure. Wild-type age-matched neonatal C57Bl/6 (WT) and SOD3(−/−) (KO) mice were placed in normoxia (21% FiO(2), RA) or chronic hyperoxia (75% FiO(2), O(2)) within 24 h of birth for 14 days continuously and then euthanized. Lungs were harvested for histologic evaluation, as well as comparison of antioxidant enzyme expression, SOD activity, VEGF expression, and portions of the NO signaling pathway. Surprisingly, KO-O(2) mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O(2) mice. KO-O(2) mice had increased total SOD activity and increased VEGF expression when compared to WT-O(2) mice. No genotype differences were noted in intracellular antioxidant enzyme expression or the NO signaling pathway. These results demonstrate that SOD3 KO mice can survive prolonged hyperoxia without exacerbation of alveolar or vascular phenotype. MDPI 2021-08-01 /pmc/articles/PMC8388997/ /pubmed/34439484 http://dx.doi.org/10.3390/antiox10081236 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mathias, Maxwell
Taylor, Joann
Mendralla, Elizabeth
Perez, Marta
Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia
title Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia
title_full Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia
title_fullStr Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia
title_full_unstemmed Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia
title_short Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia
title_sort neonatal extracellular superoxide dismutase knockout mice increase total superoxide dismutase activity and vegf expression after chronic hyperoxia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388997/
https://www.ncbi.nlm.nih.gov/pubmed/34439484
http://dx.doi.org/10.3390/antiox10081236
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