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)

We investigated a possible involvement of the prion protein in ventilatory control in four groups of mice, those deficient for the prion protein (PrP(c)), those overexpressing the prion protein, and two groups of genetically and age-matched controls. Ventilatory patterns of unrestrained mice were measured in a whole-body plethysmograph. Between each genotype and its control, we compared ventilation at rest and the ventilatory response to moderate hypoxia (10-12% O2), hyperoxia and hyperoxic hypercapnia. Mice lacking or overexpressing PrP(c) and their respective controls showed similar ventilatory patterns at rest and similar chemosensory responses when awake and under urethane anesthesia. Our results do not support the view that PrP(c) may play any significant role in basal ventilation or in the chemosensory ventilatory control of adult mice.
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PMID:Respiratory function in mice lacking or overexpressing the prion protein. 1195 May

The biological function of cellular prion protein PrPc has not been established, despite in vitro studies suggesting antioxidant activity or link to signal transduction pathways. In this study, mice were exposed to hyperoxia to establish whether oxidative stress affected prion expression in vivo. C57Bl/6J mice aged 6, 18, and 24 months, maintained under normoxic conditions, exhibited age-related increases in PrPc in both cerebral microvessels and in microvessel-depleted brain homogenate. We demonstrate that PrPc is differentially affected by exposure to hyperoxia in vivo for 1 (24 h) or 2 (48 h) days, or for 1 day hyperoxia, followed by 1 day normoxia. Brain parenchymal cells from 6-month-old mice exposed to 1 day hyperoxia showed elevation of a glycosylated approximately 36 kDa form, whereas in 24-month-old mice cellular prion level was substantially reduced. Extending hyperoxia from 1 to 2 days resulted in significantly reduced PrPc level, regardless of age. Parenchymal PrPc is substantially elevated in 6-month-old mice, but declines in 18- and 24-month-old animals following 1 day hyperoxia. By contrast, PrPc content in cerebral microvessels from 6-month-old mice declined after a 2 day exposure to hyperoxia, while microvessels from 24-month-old brains showed elevated prion levels 24 h after hyperoxia. Moreover, unglycosylated 25-30 kDa PrPc, and a previously undescribed 50-64 kDa band containing at least some glycosylated protein, predominated in microvessels with lesser content of the glycosylated approximately 36 kDa form. Cellular content of these unglycosylated forms was correlated with age, while the response to hyperoxia was evident in both unglycosylated and glycosylated forms of the protein following 1 and 2 day exposures. The observed elevation of the 25-30 and 50-64 kDa bands of microvessel PrPc is not sustainable following 1 day hyperoxia, but returns to near normoxic levels within 24 h after hyperoxia. We also show in a knockout mouse for methionine sulfoxide reductase (MsrA), the enzyme responsible for reducing methionine sulfoxide back to methionine, and a regulator of cellular antioxidant defence, that following hyperoxia brain PrPc in the null mutant is elevated relative to PrPc content in the parent strain. Our results show up-regulated PrPc expression or reduced turnover in response to age-related, and hyperoxia-induced oxidative stress.
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PMID:Ageing and exposure to oxidative stress in vivo differentially affect cellular levels of PrP in mouse cerebral microvessels and brain parenchyma. 1504 13