Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Oxidative Stress-Dependent Hypertension Associated with the Depletion of DJ-1
Hypertension, ISSN: 1524-4563, Vol: 65, Issue: 6, Page: 1251-1257
2015
- 32Citations
- 13Usage
- 20Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations32
- Citation Indexes32
- 32
- CrossRef30
- Usage13
- Abstract Views13
- Captures20
- Readers20
- 20
Article Description
Renal dopamine 2 receptor dysfunction is associated with oxidative stress and high blood pressure (BP). We have reported that DJ-1, an oxidative stress response protein, is positively regulated by dopamine 2 receptor in the kidney. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of several antioxidant genes. We tested the hypothesis that Nrf2 is involved in the renal DJ-1-mediated inhibition of reactive oxygen species production. We have reported that silencing dopamine 2 receptor in mouse renal proximal tubule cells decreases the expression of DJ-1. We now report that silencing DJ-1 or dopamine 2 receptor in mouse proximal tubule cells and mouse kidneys decreases Nrf2 expression and activity and increases reactive oxygen species production; BP is also increased in mice in which renal DJ-1 or dopamine 2 receptor is silenced. DJ-1 -/- mice have decreased renal Nrf2 expression and activity and increased nitro-tyrosine levels and BP. Silencing Nrf2 in mouse proximal tubule cells does not alter the expression of DJ-1 or dopamine 2 receptor, indicating that Nrf2 is downstream of dopamine 2 receptor and DJ-1. An Nrf2 inducer, bardoxolone, normalizes the systolic BP and renal malondialdehyde levels in DJ-1 -/- mice without affecting them in their wild-type littermates. Because Nrf2 ubiquitination is increased in DJ-1 -/- mice, we conclude that the protective effect of DJ-1 on renal oxidative stress is mediated, in part, by preventing Nrf2 degradation. Moreover, renal dopamine 2 receptor and DJ-1 are necessary for normal Nrf2 activity to keep a normal redox balance and BP.
Bibliographic Details
https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3674; https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3793
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84937561416&origin=inward; http://dx.doi.org/10.1161/hypertensionaha.114.04525; http://www.ncbi.nlm.nih.gov/pubmed/25895590; https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.114.04525; http://hyper.ahajournals.org/lookup/doi/10.1161/HYPERTENSIONAHA.114.04525; https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3674; https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=4680&context=smhs_medicine_facpubs; https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3793; https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=4799&context=smhs_medicine_facpubs; http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04525; http://hyper.ahajournals.org/content/65/6/1251; https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.114.04525; http://hyper.ahajournals.org/cgi/doi/10.1161/HYPERTENSIONAHA.114.04525
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