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)

Cystic fibrosis is a lethal inherited disorder caused by mutations in a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in progressive oxidative lung damage. In this study, we evaluated the role of CFTR in the control of ubiquitin-proteasome activity and nuclear factor (NF)-kappaB/IkappaB-alpha signaling after lung oxidative stress. After a 64-hour exposure to hyperoxia-mediated oxidative stress, CFTR-deficient (cftr(-/-)) mice exhibited significantly elevated lung proteasomal activity compared with wild-type (cftr(+/+)) animals. This was accompanied by reduced lung caspase-3 activity and defective degradation of NF-kappaB inhibitor IkappaB-alpha. In vitro, human CFTR-deficient lung cells exposed to oxidative stress exhibited increased proteasomal activity and decreased NF-kappaB-dependent transcriptional activity compared with CFTR-sufficient lung cells. Inhibition of the CFTR Cl(-) channel by CFTR(inh-172) in the normal bronchial immortalized cell line 16HBE14o- increased proteasomal degradation after exposure to oxidative stress. Caspase-3 inhibition by Z-DQMD in CFTR-sufficient lung cells mimicked the response profile of increased proteasomal degradation and reduced NF-kappaB activity observed in CFTR-deficient lung cells exposed to oxidative stress. Taken together, these results suggest that functional CFTR Cl(-) channel activity is crucial for regulation of lung proteasomal degradation and NF-kappaB activity in conditions of oxidative stress.
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PMID:Cystic fibrosis transmembrane conductance regulator controls lung proteasomal degradation and nuclear factor-kappaB activity in conditions of oxidative stress. 1837 27

This review considers the contributions to exercise hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O(2) dependent. The early phase of exercise hyperaemia is attributable to K(+) released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K(+) may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H(+). ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A(2A) receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O(2) attenuates efflux of H(+) and lactate, thereby decreasing the contribution that adenosine makes to exercise hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE(2) and PGI(2), also accumulate in the interstitium during exercise, and breathing 40% O(2) abolished the contribution of PGs to exercise hyperaemia. This suggests that PGE(2) released from muscle fibres and PGI(2) released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise hyperaemia by improving O(2) supply, limiting the release of O(2)-dependent adenosine and PGs, higher O(2) concentrations may have adverse effects. Evidence is presented that breathing 100% O(2) limits exercise hyperaemia by generating O(2)(-), which inactivates nitric oxide and decreases PG synthesis.
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PMID:Contribution of non-endothelium-dependent substances to exercise hyperaemia: are they O(2) dependent? 2304 41