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)

In mammals, disulfide isomerase associated 3, PDIA3, is a member of the endoplasmic reticulum (ER) stress proteins, which can be induced by oxidative stress; however, its role in relation to stress regulation is still unknown in fish. Here, we report the cloning of a coding region of PDIA3 from the Atlantic salmon. PDIA3 mRNA expression was evaluated in the liver of Atlantic salmon exposed to environmental hyperoxia stress and toxic perfluorooctane sulfonate (PFOS) exposure stress. The PDIA3 sequence contained two PDI-typical thioredoxin active sites of WCGHC and shared approximately 70% identity with mammalian PDIA3, and its mRNA was primarily expressed in the liver. PDIA3 was significantly increased in the liver of Atlantic salmon exposed to hyperoxic water during smoltification. Also Mn superoxide dismutase (Mn-SOD) and CCAAT/enhancer binding protein (C/EBP), other markers of oxidative stress, were upregulated by hyperoxia. Furthermore, PFOS exposure of hepatocytes resulted in elevated mRNA expression of PDIA3, Mn-SOD and C/EBPdelta as well as peroxisome proliferator-activated receptor gamma (PPARgamma). These results indicate a signaling connection between oxidative stress and ER stress. PDIA3 and C/EBPdelta may be valuable markers in fish for exposure and effect to environmental stress.
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PMID:Stress-induced expression of protein disulfide isomerase associated 3 (PDIA3) in Atlantic salmon (Salmo salar L.). 1974 60

The most common form of newborn chronic lung disease, bronchopulmonary dysplasia (BPD), is thought to be caused by oxidative disruption of lung morphogenesis, which results in decreased pulmonary vasculature and alveolar simplification. Although cellular redox status is known to regulate cellular proliferation and differentiation, redox-sensitive pathways associated with these processes in developing pulmonary epithelium are unknown. Redox-sensitive pathways are commonly regulated by cysteine thiol modifications. Therefore two thiol oxidoreductase systems, thioredoxin and glutathione, were chosen to elucidate the roles of these pathways on cell death. Studies herein indicate that thiol oxidation contributes to cell death through impaired activity of glutathione-dependent and thioredoxin (Trx) systems and altered signaling through redox-sensitive pathways. Free thiol content decreased by 71% with hyperoxic (95% oxygen) exposure. Increased cell death was observed during oxygen exposure when either the Trx or the glutathione-dependent system was pharmacologically inhibited with aurothioglucose (ATG) or buthionine sulfoximine, respectively. However, inhibition of the Trx system yielded the smallest decrease in free thiol content (1.44% with ATG treatment vs 21.33% with BSO treatment). Although Trx1 protein levels were unchanged, Trx1 function was impaired during hyperoxic treatment as indicated by progressive cysteine oxidation. Overexpression of Trx1 in H1299 cells utilizing an inducible construct increased cell survival during hyperoxia, whereas siRNA knockdown of Trx1 during oxygen treatment reduced cell viability. Overall, this indicated that a comparatively small pool of proteins relies on Trx redox functions to mediate cell survival in hyperoxia, and the protective functions of Trx1 are progressively lost by its oxidative inhibition. To further elucidate the role of Trx1, potential Trx1 redox protein-protein interactions mediating cytoprotection and cell survival pathways were determined by utilizing a substrate trap (mass action trapping) proteomics approach. With this method, known Trx1 targets were detected, including peroxiredoxin-1as well as novel targets, including two HSP90 isoforms (HSP90AA1 and HSP90AB1). Reactive cysteines within the structure of HSP90 are known to modulate its ATPase-dependent chaperone activity through disulfide formation and S-nitrosylation. Whereas HSP90 expression is unchanged at the protein level during hyperoxic exposure, siRNA knockdown significantly increased hyperoxic cell death by 2.5-fold, indicating cellular dependence on HSP90 chaperone functions in response to hyperoxic exposure. These data support the hypothesis that hyperoxic impairment of Trx1 has a negative impact on HSP90-oxidative responses critical to cell survival, with potential implications for pathways implicated in lung development and the pathogenesis of BPD.
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PMID:Thioredoxin-1 redox signaling regulates cell survival in response to hyperoxia. 2510 6