Oxidative stress and inflammation modulate Rev-erbα signaling in the neonatal lung and affect circadian rhythmicity
| Autor: | Guang Yang, Clyde J. Wright, Amal P. Fernando, Shaon Sengupta, Phyllis A. Dennery, Ping La, Chhanda Biswas, Maurice D. Hinson |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Physiology DNA damage Cell Survival Clinical Biochemistry Inflammation Biology medicine.disease_cause Biochemistry Mice Transcription (biology) Internal medicine medicine Animals Circadian rhythm RNA Messenger Molecular Biology Lung Cells Cultured General Environmental Science Hyperoxia Binding Sites NF-kappa B Cell Biology Hydrogen Peroxide NFKB1 Circadian Rhythm Mice Inbred C57BL Oxidative Stress Original Research Communications Endocrinology Animals Newborn Nuclear Receptor Subfamily 1 Group D Member 1 General Earth and Planetary Sciences Comet Assay medicine.symptom Signal transduction Oxidative stress DNA Damage Signal Transduction |
| Zdroj: | Antioxidantsredox signaling. 21(1) |
| ISSN: | 1557-7716 |
| Popis: | Aims: The response to oxidative stress and inflammation varies with diurnal rhythms. Nevertheless, it is not known whether circadian genes are regulated by these stimuli. We evaluated whether Rev-erbα, a key circadian gene, was regulated by oxidative stress and/or inflammation in vitro and in a mouse model. Results: A unique sequence consisting of overlapping AP-1 and nuclear factor kappa B (NFκB) consensus sequences was identified on the mouse Rev-erbα promoter. This sequence mediates Rev-erbα promoter activity and transcription in response to oxidative stress and inflammation. This region serves as an NrF2 platform both to receive oxidative stress signals and to activate Rev-erbα, as well as an NFκB-binding site to repress Rev-erbα with inflammatory stimuli. The amplitude of the rhythmicity of Rev-erbα was altered by pre-exposure to hyperoxia or disruption of NFκB in a cell culture model of circadian simulation. Oxidative stress overcame the inhibitory effect of NFκB binding on Rev-erbα transcription. This was confirmed in neonatal mice exposed to hyperoxia, where hyperoxia-induced lung Rev-erbα transcription was further increased with NFκB disruption. Interestingly, this effect was not observed in similarly exposed adult mice. Innovation: These data provide novel mechanistic insights into how key circadian genes are regulated by oxidative stress and inflammation in the neonatal lung. Conclusion: Rev-erbα transcription and circadian oscillation are susceptible to oxidative stress and inflammation in the neonate. Due to Rev-erbα's role in cellular metabolism, this could contribute to lung cellular function and injury from inflammation and oxidative stress. Antioxid. Redox Signal. 21, 17–32. |
| Databáze: | OpenAIRE |
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