Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well established that hyperoxia injures and kills alveolar endothelial and type I epithelial cells of the lung. Although type II epithelial cells remain morphologically intact, it remains unclear whether they are also damaged. DNA integrity was investigated in adult mice whose type II cells were identified by their endogenous expression of pro-surfactant protein C or transgenic expression of enhanced green fluorescent protein. In mice exposed to room air, punctate perinuclear 8-oxoguanine staining was detected in approximately 4% of all alveolar cells and in 30% of type II cells. After 48 or 72 h of hyperoxia, 8-oxoguanine was detected in 11% of all alveolar cells and in >60% of type II cells. 8-Oxoguanine colocalized by confocal microscopy with the mitochondrial transmembrane protein cytochrome oxidase subunit 1. Type II cells isolated from hyperoxic lungs exhibited nuclear DNA strand breaks by comet assay even though they were viable and morphologically indistinguishable from cells isolated from lungs exposed to room air. These data reveal that type II cells exposed to in vivo hyperoxia have oxidized and fragmented DNA. Because type II cells are essential for lung remodeling, our findings raise the possibility that they are proficient in DNA repair.
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PMID:In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells. 1472 12

Glycoprotein nonmetastatic melanoma protein B (GPNMB), a transmembrane protein, has been reported to have an important role in tissue repair and angiogenesis. Recently, we have demonstrated that hyperoxia exposure down-regulates microRNA (miR)-150 expression and concurrent induction of its target gene, GPNMB, in neonatal rat lungs. This study aimed to test the hypothesis that soluble GPNMB (sGPNMB) promotes angiogenesis in the hyperoxic neonatal lungs. Wild-type (WT) or miR-150 knockout (KO) neonates, exposed to 95% O2 for 3, 6, and 10 days, were evaluated for lung phenotypes, GPNMB protein expression in the lungs, and sGPNMB levels in the bronchoalveolar lavage. Angiogenic effects of sGPNMB were examined both in vitro and in vivo. After a 6-day exposure, similar analyses were performed in WT and miR-150 KO neonates during recovery at 7, 14, and 21 days. miR-150 KO neonates displayed an increased capillary network, decreased inflammation, and less alveolar damage compared with WT neonates after hyperoxia exposure. The early induction of GPNMB and sGPNMB were found in miR-150 KO neonates. The recombinant GPNMB, which contained a soluble portion of GPNMB, promoted endothelial tube formation in vitro and enhanced angiogenesis in vivo. The increased capillaries in the hyperoxic lungs of miR-150 KO neonates appeared dysmorphic. They were abnormally enlarged in size and occasionally laid at subepithelial regions in the alveoli. However, the lung architecture returned to normal during recovery, suggesting that abnormal vascularity during hyperoxia does not affect postnatal lung development. GPNMB plays an important role in angiogenesis during hyperoxia injury. Treatment with GPNMB may offer a novel therapeutic approach in reducing pathologic complications in bronchopulmonary dysplasia.
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PMID:Role of microRNA-150 and glycoprotein nonmetastatic melanoma protein B in angiogenesis during hyperoxia-induced neonatal lung injury. 2505 12