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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar development comprises the transition of lung architecture from saccules to gas-exchange units during late gestation and early postnatal development. Exposure to hyperoxia disrupts developmental signaling pathways and causes alveolar hypoplasia as seen in bronchopulmonary dysplasia affecting preterm human newborns. Expanding literature suggests that epigenetic changes caused by environmental triggers during development may lead to heritable changes in gene expression. Given recent data on altered histone deacetylase (HDAC) activity in lungs of humans and animal models with airspace enlargement/emphysema, we hypothesized that alveolar hypoplasia from hyperoxia exposure in neonatal mice is a consequence of cell cycle arrest and reduced HDAC activity and up-regulation of the cyclin-dependent kinase inhibitor, p21. We exposed newborn mice to hyperoxia and compared lung morphologic and epigenetic changes to room air controls. Furthermore, we pretreated a subgroup of animals with the macrolide antibiotic azithromycin (AZM), known to possess antiinflammatory properties. Our results showed that hyperoxia exposure resulted in alveolar hypoplasia and was associated with decreased HDAC1 and HDAC2 and increased p53 and p21 expression. Furthermore, AZM did not confer protection against hyperoxia-induced alveolar changes. These findings suggest that alveolar hypoplasia caused by hyperoxia is mediated by epigenetic changes affecting cell cycle regulation/senescence during lung development.
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PMID:Hyperoxia impairs alveolar formation and induces senescence through decreased histone deacetylase activity and up-regulation of p21 in neonatal mouse lung. 2127 Jun 77

Bronchopulmonary dysplasia (BPD) poses a significant global health problem. It mainly occurs in preterm infants. It is histopathologically characterized by fewer and larger alveoli and less secondary septa, suggesting an arrested or disordered lung development. To date, the mechanisms that lead to the pathophysiological changes in BPD have still not been totally understood. In embryonic development, histone deacetylase (HDAC) plays an important role by regulating gene transcription. Here, we hypothesize that a decreased HDAC expression and activity, caused by preterm birth or environmental stresses, contribute to a disorder in alveolar development in BPD. To this end, newborn Sprague-Dawley rats subjected to hyperoxia (85% O(2) ) were used to investigate the gene expression and protein activity of HDAC and alveolar development in lungs. Our results showed that hyperoxia exposure led to a suppression of the HDAC1/HDAC2 expression and activity, and the overall HDAC activity, as well as arrest of alveolarization, and an elevated expression of the cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the lungs of newborn rats. However, preservation of HDAC activity by theophylline significantly improved alveolar development and attenuated CINC-1 release, all of which were blocked by a specific HDAC inhibitor, trichostatin A (TSA). TSA alone can disturb the alveolar development in neonatal rats. Our findings indicate that a persistent exposure to hyperoxia leads to a suppressed HDAC activity, which causes disorders in pulmonary development. This effect may be mediated by CINC-1. Attenuation of CINC-1-mediated inflammation by activating HDAC may have a protective effect in BPD.
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PMID:Hyperoxia arrests alveolar development through suppression of histone deacetylases in neonatal rats. 2190 65