SOD2 Activity Is not Impacted by Hyperoxia in Murine Neonatal Pulmonary Artery Smooth Muscle Cells and Mice
Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Chicago, IL 60611, USA
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Author to whom correspondence should be addressed.
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These authors contributed equally to this work.
Academic Editor: Gabor Csanyi
Int. J. Mol. Sci. 2015, 16(3), 6373-6390; https://doi.org/10.3390/ijms16036373
Received: 30 January 2015 / Revised: 9 March 2015 / Accepted: 12 March 2015 / Published: 19 March 2015
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Pulmonary hypertension (PH) complicates bronchopulmonary dysplasia (BPD) in 25% of infants. Superoxide dismutase 2 (SOD2) is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice and isogenic SOD2+/+ and SOD2−/+ mice were placed in room air (control) or 75% O2 (chronic hyperoxia, CH) for 14 days. Right ventricular hypertrophy (RVH) was assessed by Fulton’s index. Medial wall thickness (MWT) and alveolar area were assessed on formalin fixed lung sections. Pulmonary artery smooth muscle cells (PASMC) were placed in 21% or 95% O2 for 24 h. Lung and PASMC protein were analyzed for SOD2 expression and activity. Oxidative stress was measured with a mitochondrially-targeted sensor, mitoRoGFP. CH lungs have increased SOD2 expression, but unchanged activity. SOD2−/+ PASMC have decreased expression and activity at baseline, but increased SOD2 expression in hyperoxia. Hyperoxia increased mitochondrial ROS in SOD2+/+ and SOD2−/+ PASMC. SOD2+/+ and SOD2−/+ CH pups induced SOD2 expression, but not activity, and developed equivalent increases in RVH, MWT, and alveolar area. Since SOD2−/+ mice develop equivalent disease, this suggests other antioxidant systems may compensate for partial SOD2 expression and activity in the neonatal period during hyperoxia-induced oxidative stress.
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Keywords:
bronchopulmonary dysplasia; superoxide dismutase 2 (SOD2); right ventricular hypertrophy; pulmonary hypertension
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MDPI and ACS Style
Gupta, A.; Perez, M.; Lee, K.J.; Taylor, J.M.; Farrow, K.N. SOD2 Activity Is not Impacted by Hyperoxia in Murine Neonatal Pulmonary Artery Smooth Muscle Cells and Mice. Int. J. Mol. Sci. 2015, 16, 6373-6390.
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