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

Epidermal growth factor (EGF) has been shown to accelerate fetal lung maturation in rabbits, lambs, and rhesus monkeys in vivo and increase surfactant synthesis in vitro. Its effect on the maturation of the lung antioxidant enzyme system, however, is unknown. We studied the effect of EGF (10 nM) on 19-d fetal rat lung explant cultures in serum-free medium in air/5% CO2 or > 90% O2/5% CO2 compared with similarly grown control cultures in air or hyperoxia at 72 h. Fetal lung activities of superoxide dismutase and catalase were unchanged by EGF in air, whereas glutathione peroxidase activity was significantly decreased (p < 0.05 versus air control). However, in hyperoxia, EGF-treated fetal lung cultures had significantly elevated superoxide dismutase and catalase activities (p < 0.01) versus O2-exposed controls, and glutathione peroxidase activity similar to that of controls. The mRNA levels for all the antioxidant enzymes showed patterns similar to the enzyme activities except in the case of Cu,Zn-superoxide dismutase mRNA, which increased in EGF-air cultures. EGF decreased the rate of 3H-choline incorporation into disaturated phosphatidylcholine in air (p < 0.01 versus air control), but increased disaturated phosphatidylcholine synthesis in response to hyperoxia (p < 0.01 versus O2 control). The histologic appearance of EGF-treated cultures in O2 was superior to that of O2-exposed controls, which showed thickened septal walls, decreased surfactant in the air spaces, and epithelial cell mitochondrial swelling. EGF therefore accelerates antioxidant enzyme and disaturated phosphatidylcholine maturation under hyperoxic conditions and protects fetal rat lung cultures from hyperoxic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epidermal growth factor increases antioxidant enzyme and surfactant system development during hyperoxia and protects fetal rat lungs in vitro from hyperoxic toxicity. 828 92

Hyperoxia is one of the major contributors to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants. Emerging evidence suggests that the arrested lung development of BPD is associated with pulmonary endothelial cell death and vascular dysfunction resulting from hyperoxia-induced lung injury. A better understanding of the mechanism of hyperoxia-induced endothelial cell death will provide critical information for the pathogenesis and therapeutic development of BPD. Epidermal growth factor-like domain 7 (EGFL7) is a protein secreted from endothelial cells. It plays an important role in vascular tubulogenesis. In the present study, we found that Egfl7 gene expression was significantly decreased in the neonatal rat lungs after hyperoxic exposure. The Egfl7 expression was returned to near normal level 2 wk after discounting oxygen exposure during recovery period. In cultured human endothelial cells, hyperoxia also significantly reduced Egfl7 expression. These observations suggest that diminished levels of Egfl7 expression might be associated with hyperoxia-induced endothelial cell death and lung injury. When we overexpressed human Egfl7 (hEgfl7) in EA.hy926 human endothelial cell line, we found that hEgfl7 overexpression could partially block cytochrome c release from mitochondria and decrease caspase-3 activation. Further Western blotting analyses showed that hEgfl7 overexpression could reduce expression of a proapoptotic protein, Bax, and increase expression of an antiapoptotic protein, Bcl-xL. Theses findings indicate that hEGFL7 may protect endothelial cell from hyperoxia-induced apoptosis by inhibition of mitochondria-dependent apoptosis pathway.
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PMID:Epidermal growth factor-like domain 7 protects endothelial cells from hyperoxia-induced cell death. 1799 82