Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-124 |
Sentence |
denotes |
NADPH oxidase and ERK signaling regulates hyperoxia-induced Nrf2-ARE transcriptional response in pulmonary epithelial cells. |
T2 |
125-200 |
Sentence |
denotes |
Oxidative stress plays a major role in hyperoxia-induced acute lung injury. |
T3 |
201-311 |
Sentence |
denotes |
We have shown previously that mice lacking the Nrf2 are more susceptible to hyperoxia than are wild-type mice. |
T4 |
312-441 |
Sentence |
denotes |
Nrf2 activates antioxidant response element (ARE)-mediated gene expression involved in cellular protection against toxic insults. |
T5 |
442-616 |
Sentence |
denotes |
The present study was designed to investigate the mechanisms that control the activation of Nrf2 by hyperoxia using a non-malignant murine alveolar epithelial cell line, C10. |
T6 |
617-724 |
Sentence |
denotes |
No significant alteration in the levels of Nrf2 mRNA and protein was found following exposure to hyperoxia. |
T7 |
725-844 |
Sentence |
denotes |
In contrast, hyperoxia caused the translocation of Nrf2 from the cytoplasm to the nucleus within 30-60 min of exposure. |
T8 |
845-1053 |
Sentence |
denotes |
Consistent with these observations, gel shift and reporter analyses demonstrated a correlation between the hyperoxia-enhanced ARE DNA-binding activity of Nrf2 and an up-regulation of ARE-driven transcription. |
T9 |
1054-1176 |
Sentence |
denotes |
Inhibition of NADPH oxidase with diphenyleneiodonium (DPI) blocked both Nrf2 translocation and ARE-mediated transcription. |
T10 |
1177-1235 |
Sentence |
denotes |
Inhibition of the MEK/ERK pathway caused a similar effect. |
T11 |
1236-1379 |
Sentence |
denotes |
Consistent with this finding, hyperoxia stimulated ERK-1 and ERK-2 phosphorylation, whereas DPI or N-acetyl-l-cysteine blocked such activation. |
T12 |
1380-1546 |
Sentence |
denotes |
Hyperoxia stimulated the phosphorylation of endogenous Nrf2, but not in the presence of U0126, suggesting a critical role for ERK signaling in the activation of Nrf2. |
T13 |
1547-1665 |
Sentence |
denotes |
Consistent with this notion, hyperoxia did not stimulate the phosphorylation of Nrf2 in fibroblasts lacking the ERK-1. |
T14 |
1666-1817 |
Sentence |
denotes |
Collectively, our findings suggest that hyperoxia-induced, ARE-driven, Nrf2-dependent transcription is controlled by NADPH oxidase and ERK-1 signaling. |