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)

Rats (200-260 g) were exposed in sealed, recycling chambers continuously for 2-30 days to gas mixtures designed to maintain the same alveolar PO2 in the presence or absence of inert gas. Mixtures with inert gas (N2, He, or Ne) were at ground level; those without inert gas (100 percent O2) were in an altitude chamber. The O2 categories were: I-100 percent O2 at 747 torr; II-74 percent O2 + 26 percent inert and 566 torr 100 percent O2; III-47 percent O2 + 53 percent inert and 381 torr 100 percent O2; IV-21 percent O2 + 79 percent inert and 197 torr 100 percent O2. One of the two room-air controls was "restricted-fed" to the level of the lowest intake group. Measurements included body, pituitary, and thyroid weight, food and water intake, plasma volume and hematocrit, pituitary and plasma TSH, and plasma PBI. Severe depression in all variables and over 50 percent mortality was seen in I by day 4. All variables were depressed in II, but there was no mortality to 20 days. Pituitary-thyroid function appeared to be particularly sensitive to depression by hyperoxia, with plasma TSH levels reduced between 42 and 60 percent in II and III. No effect was attributable to the inert gas, whether it was N2, He, or Ne, nor was any specific effect traceable to the presence or absence of inert gas.
 ...
PMID:Pituitary-thyroid function of rats in hypobaric oxygen-inert gas environments. 80 43

Lung epithelial cell death is a prominent feature of hyperoxic lung injury, and has been considered a very important underlying mechanism of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Here we report on a novel mechanism involved in epithelial cytoprotection and homeostasis after oxidative stress. p62 (sequestosome 1; SQSTM1) is a ubiquitously expressed cellular protein. It interacts with ubiquitinated proteins and autophagic marker light chain 3b (LC3b), thus mediating the degradation of selective targets. In this study, we explored the role of p62 in mitochondria-mediated cell death after hyperoxia. Lung alveolar epithelial cells demonstrate abundant p62 expression, and p62 concentrations are up-regulated by oxidative stress at both the protein and mRNA levels. The p62/LC3b complex interacts with Fas and truncated BID (tBID) physically. These interactions abruptly diminish after hyperoxia. The deletion of p62 robustly increases tBID and cleaved caspase-3, implying an antiapoptotic effect. This antiapoptotic effect of p62 is further confirmed by measuring caspase activities, cleaved poly ADP ribose polymerase, and cell viability. The deletion of the p62 PBI domain or the ubiquitin-associated domain both lead to elevated tBID, cleaved caspase-3, and significantly more cell death after hyperoxia. Moreover, p62 traffics in an opposite direction with LC3b after hyperoxia, leading to the dissociation of the p62/Cav-1/LC3b/BID complex. Subsequently, the LC3b-mediated lysosomal degradation of tBID is eliminated. Taken together, our data suggest that the p62/LC3b complex regulates lung alveolar epithelial cell homeostasis and cytoprotection after hyperoxia.
 ...
PMID:p62 sequestosome 1/light chain 3b complex confers cytoprotection on lung epithelial cells after hyperoxia. 2333 19