{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:23:34Z","timestamp":1788870214140,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL109478"],"award-info":[{"award-number":["HL109478"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NCI CA060553"],"award-info":[{"award-number":["NCI CA060553"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212\/+ mice were placed in room air (control) or 75% O2 (chronic hyperoxia, CH) for 14 days. Right ventricular hypertrophy (RVH) was assessed by Fulton\u2019s 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\u2212\/+ PASMC have decreased expression and activity at baseline, but increased SOD2 expression in hyperoxia. Hyperoxia increased mitochondrial ROS in SOD2+\/+ and SOD2\u2212\/+ PASMC. SOD2+\/+ and SOD2\u2212\/+ CH pups induced SOD2 expression, but not activity, and developed equivalent increases in RVH, MWT, and alveolar area. Since SOD2\u2212\/+ 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.<\/jats:p>","DOI":"10.3390\/ijms16036373","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T10:38:57Z","timestamp":1426761537000},"page":"6373-6390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["SOD2 Activity Is not Impacted by Hyperoxia in Murine Neonatal Pulmonary Artery Smooth Muscle Cells and Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Anita","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joann","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Farrow","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1542\/peds.2007-0971","article-title":"Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: Clinical features and outcomes in the surfactant era","volume":"120","author":"Khemani","year":"2007","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1053\/j.semperi.2013.01.009","article-title":"Pulmonary hypertension in bronchopulmonary dysplasia","volume":"37","author":"Berkelhamer","year":"2013","journal-title":"Semin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/jp.2012.164","article-title":"Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia","volume":"33","author":"Check","year":"2013","journal-title":"J. Perinatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/jp.2013.75","article-title":"Therapeutic interventions and short-term outcomes for infants with severe bronchopulmonary dysplasia born at <32 weeks\u2019 gestation","volume":"33","author":"Padula","year":"2013","journal-title":"J. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4070\/kcj.2010.40.3.131","article-title":"Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia","volume":"40","author":"An","year":"2010","journal-title":"Korean Circ. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/jp.2014.35","article-title":"Predicting death or tracheostomy placement in infants with severe bronchopulmonary dysplasia","volume":"34","author":"Murthy","year":"2014","journal-title":"J. Perinatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.resp.2010.08.018","article-title":"Mitochondrial oxidant stress increases PED5 activity in persistent pulmonary hypertension of the newborn","volume":"174","author":"Farrow","year":"2010","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1089\/ars.2011.4184","article-title":"Brief hyperoxia increases mitochondrial oxidation and increases phosphodiesterase 5 activity in fetal pulmonary artery smooth muscle cells","volume":"17","author":"Farrow","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1161\/CIRCRESAHA.107.161463","article-title":"Hyperoxia increases phosphodiesterase 5 expression and activity in ovine fetal pulmonary artery smooth muscle cells","volume":"102","author":"Farrow","year":"2008","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1165\/rcmb.2013-0118OC","article-title":"Disrupted pulmonary artery cyclic guanosine monophosphate signaling in mice with hyperoxia-induced pulmonary hypertension","volume":"50","author":"Lee","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"C840","DOI":"10.1152\/ajpcell.1998.275.3.C840","article-title":"Tissue distribution of immunoreactive mouse extracellular superoxide dismutase","volume":"275","author":"Ookawara","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"L32","DOI":"10.1152\/ajplung.00133.2005","article-title":"Transgenic extracellular superoxide dismutase protects postnatal alveolar epithelial proliferation and development during hyperoxia","volume":"290","author":"Auten","year":"2006","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1542\/peds.111.3.469","article-title":"Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human cuzn superoxide dismutase","volume":"111","author":"Davis","year":"2003","journal-title":"Pediatrics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0891-5849(95)91457-3","article-title":"The definition and measurement of antioxidants in biological systems","volume":"18","author":"Halliwell","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23937","DOI":"10.1016\/S0021-9258(18)35927-1","article-title":"Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury","volume":"267","author":"Wispe","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1016\/S0047-6374(01)00298-6","article-title":"Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta","volume":"122","author":"Guo","year":"2001","journal-title":"Mech. Ageing Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/019021499270060","article-title":"Survival, lung injury, and lung protein nitration in heterozygous mnsod knockout mice in hyperoxia","volume":"25","author":"Jackson","year":"1999","journal-title":"Exp. Lung Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"L1073","DOI":"10.1152\/ajplung.00347.2006","article-title":"Hyperoxia reduces bone marrow, circulating, and lung endothelial progenitor cells in the developing lung: Implications for the pathogenesis of bronchopulmonary dysplasia","volume":"292","author":"Balasubramaniam","year":"2007","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1164\/rccm.200902-0242OC","article-title":"Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease","volume":"180","author":"Aslam","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","first-page":"131","article-title":"Postnatal growth of the mouse lung","volume":"124","author":"Amy","year":"1977","journal-title":"J. Anat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9782","DOI":"10.1073\/pnas.93.18.9782","article-title":"Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice","volume":"93","author":"Lebovitz","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cardfail.2005.01.007","article-title":"Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium","volume":"11","author":"Sam","year":"2005","journal-title":"J. Card. Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/cvr\/cvp092","article-title":"Different extent of cardiac malfunction and resistance to oxidative stress in heterozygous and homozygous manganese-dependent superoxide dismutase-mutant mice","volume":"82","author":"Loch","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"28510","DOI":"10.1074\/jbc.273.43.28510","article-title":"Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice","volume":"273","author":"Williams","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1073\/pnas.051627098","article-title":"Increased mitochondrial oxidative stress in the SOD2+\/\u2212 mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis","volume":"98","author":"Kokoszka","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.freeradbiomed.2010.01.009","article-title":"Hypoxic neonatal pulmonary arterial myocytes are sensitized to ROS-generated 8-isoprostane","volume":"48","author":"Gong","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1165\/ajrcmb.19.1.3066","article-title":"Susceptibility of heterozygous mnsod gene-knockout mice to oxygen toxicity","volume":"19","author":"Tsan","year":"1998","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, K.J., Czech, L., Waypa, G.B., and Farrow, K.N. (2013). Isolation of pulmonary artery smooth muscle cells from neonatal mice. J. Vis. Exp., 80.","DOI":"10.3791\/50889-v"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"L979","DOI":"10.1152\/ajplung.90238.2008","article-title":"Superoxide dismutase restores enos expression and function in resistance pulmonary arteries from neonatal lambs with persistent pulmonary hypertension","volume":"295","author":"Farrow","year":"2008","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1089\/ars.2012.4766","article-title":"Increased p22phox\/Nox4 expression is involved in remodeling through hydrogen peroxide signaling in experimental persistent pulmonary hypertension of the newborn","volume":"18","author":"Wedgwood","year":"2013","journal-title":"Antioxid. Redox Signal."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/3\/6373\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:43:41Z","timestamp":1760215421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/3\/6373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,19]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3]]}},"alternative-id":["ijms16036373"],"URL":"https:\/\/doi.org\/10.3390\/ijms16036373","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,19]]}}}