Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia.
Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia.
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DOI：
10.3390/antiox10081236
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发表时间：
2021-08-01
期刊：
影响因子：
--
通讯作者：
Perez M
中科院分区：
文献类型：
--
作者：
Mathias M;Taylor J;Mendralla E;Perez M
支气管肺发育不良（BPD）是一种影响早产儿的常见肺部疾病，在暴露于补充氧和活性氧中间体后发生。细胞外超氧化物歧化酶（SOD 3）是一种处理超氧化物自由基的酶，并且已显示促进血管内皮细胞中的血管内皮生长因子（VEGF）和一氧化氮（NO）信号传导。我们利用新生儿高氧肺损伤小鼠模型和SOD 3基因敲除（KO）小鼠来评估其在慢性高氧暴露期间的功能。将野生型年龄匹配的新生C57 Bl/6（WT）和SOD 3 −/−（KO）小鼠在出生后24小时内连续14天置于常氧（21% FiO 2，RA）或慢性高氧（75% FiO 2，O2）中，然后实施安乐死。收获肺进行组织学评价，以及比较抗氧化酶表达、SOD活性、VEGF表达和NO信号通路的部分。令人惊讶的是，与WT-O2小鼠相比，KO-O2小鼠在没有额外的肺泡简化、微血管重塑或核氧化的情况下存活。与WT-O2小鼠相比，KO-O2小鼠的总SOD活性增加，VEGF表达增加。细胞内抗氧化酶表达或NO信号通路无基因型差异。这些结果表明，SOD 3基因敲除小鼠可以在长期高氧下存活，而不会加重肺泡或血管表型。
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% FiO2, RA) or chronic hyperoxia (75% FiO2, O2) 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-O2 mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O2 mice. KO-O2 mice had increased total SOD activity and increased VEGF expression when compared to WT-O2 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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DOI：
10.1152/ajplung.00176.2014
发表时间：
2015-08-15
影响因子：
4.9
作者：
Datta, Ankur;Kim, Gina A.;Berkelhamer, Sara K.
通讯作者：
Berkelhamer, Sara K.
影响因子：
7.4
作者：
Berkelhamer, Sara K.;Kim, Gina A.;Radder, Josiah E.;Wedgwood, Stephen;Czech, Lyubov;Steinhorn, Robin H.;Schumacker, Paul T.
通讯作者：
Schumacker, Paul T.
影响因子：
3.6
作者：
AUTOR, AP;FRANK, L;ROBERTS, RJ
通讯作者：
ROBERTS, RJ
DOI：
10.1073/pnas.79.24.7634
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
MARKLUND, SL
通讯作者：
MARKLUND, SL
SOD2活性不会受到鼠新生儿肺动脉平滑肌细胞和小鼠的高氧影响。
影响因子：
5.6
作者：
Gupta A;Perez M;Lee KJ;Taylor JM;Farrow KN
通讯作者：
Farrow KN