ArticleAntioxidants & redox signaling2012
Brief hyperoxia increases mitochondrial oxidation and increases phosphodiesterase 5 activity in fetal pulmonary artery smooth muscle cells.
Article in Antioxidants & redox signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Role of ROS, soluble guanylate cyclase and cGMP in mouse lung development during hyperoxia.American journal of physiology. Heart and circulatory physiology · 2026Article
- How hyperoxia affects systemic redox state: insights from PULSE-Ox, a randomised double-blind mechanistic feasibility trial.BJA open · 2026Article
- RCCD1 promotes breast carcinogenesis through regulating hypoxia-associated mitochondrial homeostasis.Oncogene · 2023Article
- Pulmonary vasodilator strategies in neonates with acute hypoxemic respiratory failure and pulmonary hypertension.Seminars in fetal & neonatal medicine · 2022Review
- Pulmonary hypertension and oxidative stress: Where is the link?Seminars in fetal & neonatal medicine · 2022Review
- Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats.Sexual medicine · 2022Article
- Novel use of riociguat in infants with severe pulmonary arterial hypertension unable to wean from inhaled nitric oxide.Frontiers in pediatrics · 2022Article
- Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment.Comprehensive Physiology · 2021Article
- Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice.Scientific reports · 2020Article
- Hydrogen sulfide, oxygen, and calcium regulation in developing human airway smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice.bioRxiv : the preprint server for biology · 2020Article
- Therapies that enhance pulmonary vascular NO-signaling in the neonate.Nitric oxide : biology and chemistry · 2020Review
- Optimal oxygenation and role of free radicals in PPHN.Free radical biology & medicine · 2019Review
- Oxygen radical disease in the newborn, revisited: Oxidative stress and disease in the newborn period.Free radical biology & medicine · 2019Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Influence of Sex on Gestational Complications, Fetal-to-Neonatal Transition, and Postnatal Adaptation.Frontiers in pediatrics · 2018Review
- Persistent Pulmonary Hypertension in the Newborn.Children (Basel, Switzerland) · 2017Review
- Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension.PloS one · 2017Article
- Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress.Biochimica et biophysica acta · 2016Review
- Hypoxia and hyperoxia potentiate PAF receptor-mediated effects in newborn ovine pulmonary arterial smooth muscle cells: significance in oxygen therapy of PPHN.Physiological reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
aimsOxygen is a pulmonary vasodilator, but data suggest high O(2) concentrations impede that response. We previously reported 24 h of 100% O(2) increased phosphodiesterase 5 (PDE5) activity in fetal pulmonary artery smooth muscle cells (FPASMC) and in ventilated neonatal lambs. PDE5 degrades cyclic GMP (cGMP) and inhibits nitric oxide (NO)-mediated cGMP-dependent vasorelaxation. We sought to determine the mechanism by which hyperoxia initiates reactive oxygen species (ROS) production and regulates PDE5.
resultsThirty minutes of hyperoxia increased mitochondrial ROS versus normoxia (30.3±1.7% vs. 21.1±2.8%), but had no effect on cytosolic ROS, measured by roGFP, a ratiometric protein thiol redox sensor. Hyperoxia increased PDE5 activity (220±39%) and decreased cGMP responsiveness to NO (37±17%). Mitochondrial catalase overexpression attenuated hyperoxia-induced mitochondrial roGFP oxidation, compared to FPASMC infected with empty adenoviral vector (50±3% of control) or mitochondrial superoxide dismutase. MitoTEMPO, mitochondrial catalase, and DT-3, a cGMP-dependent protein kinase I alpha inhibitor, decreased PDE5 activity (32±13%, 26±21%, and 63±10% of control, respectively), and restored cGMP responsiveness to NO (147±16%,172±29%, and 189±43% of control, respectively). C57Bl6 mice exposed to 90%-100% O(2) for 45 min±mechanical ventilation had increased PA PDE5 activity (206±39% and 235±75%, respectively). INNOVATION: This is the first description that hyperoxia induces ROS in the mitochondrial matrix prior to the cytosol. Our results indicate that short hyperoxia exposures can produce significant changes in critical cellular signaling pathways.
conclusionsThese results indicate that mitochondrial matrix oxidant signals generated during hyperoxia, specifically H(2)O(2), activate PDE5 in a cGMP-dependent protein kinase-dependent manner in pulmonary vascular smooth muscle cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.