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The NRF2 Activation and Antioxidative Response Are Not Impaired Overall during Hyperoxia-Induced Lung Epithelial Cell Death
Joint Authors
Potteti, Haranatha R.
Kalvakolanu, Dhananjaya V.
Reddy, Narsa M.
Reddy, Sekhar P.
Hei, Tom K.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-04-28
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Lung epithelial and endothelial cell death caused by pro-oxidant insults is a cardinal feature of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients.
The NF-E2-related factor 2 (NRF2) activation in response to oxidant exposure is crucial to the induction of several antioxidative and cytoprotective enzymes that mitigate cellular stress.
Since prolonged exposure to hyperoxia causes cell death, we hypothesized that chronic hyperoxia impairs NRF2 activation, resulting in cell death.
To test this hypothesis, we exposed nonmalignant small airway epithelial cells (AECs) to acute (1–12 h) and chronic (36–48 h) hyperoxia and evaluated cell death, NRF2 nuclear accumulation and target gene expression, and NRF2 recruitment to the endogenous HMOX1 and NQO1 promoters.
As expected, hyperoxia gradually induced death in AECs, noticeably and significantly by 36 h; ~60% of cells were dead by 48 h.
However, we unexpectedly found increased expression levels of NRF2-regulated antioxidative genes and nuclear NRF2 in AECs exposed to chronic hyperoxia as compared to acute hyperoxia.
Chromatin Immunoprecipitation (ChIP) assays revealed an increased recruitment of NRF2 to the endogenous HMOX1 and NQO1 promoters in AECs exposed to acute or chronic hyperoxia.
Thus, our findings demonstrate that NRF2 activation and antioxidant gene expression are functional during hyperoxia-induced lung epithelial cell death and that chronic hyperoxia does not impair NRF2 signaling overall.
American Psychological Association (APA)
Potteti, Haranatha R.& Reddy, Narsa M.& Hei, Tom K.& Kalvakolanu, Dhananjaya V.& Reddy, Sekhar P.. 2013. The NRF2 Activation and Antioxidative Response Are Not Impaired Overall during Hyperoxia-Induced Lung Epithelial Cell Death. Oxidative Medicine and Cellular Longevity،Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-499028
Modern Language Association (MLA)
Potteti, Haranatha R.…[et al.]. The NRF2 Activation and Antioxidative Response Are Not Impaired Overall during Hyperoxia-Induced Lung Epithelial Cell Death. Oxidative Medicine and Cellular Longevity No. 2013 (2013), pp.1-11.
https://search.emarefa.net/detail/BIM-499028
American Medical Association (AMA)
Potteti, Haranatha R.& Reddy, Narsa M.& Hei, Tom K.& Kalvakolanu, Dhananjaya V.& Reddy, Sekhar P.. The NRF2 Activation and Antioxidative Response Are Not Impaired Overall during Hyperoxia-Induced Lung Epithelial Cell Death. Oxidative Medicine and Cellular Longevity. 2013. Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-499028
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-499028