| Autor: |
Ying Xin, Yang Bai, Xin Jiang, Shanshan Zhou, Yuehui Wang, Kupper A. Wintergerst, Taixing Cui, Honglei Ji, Yi Tan, Lu Cai |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 15, Iss C, Pp 405-417 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2017.12.016 |
| Popis: |
Aims: Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by sulforaphane (SFN) protects from, and deletion of the Nrf2 gene exaggerates, diabetic cardiomyopathy. Angiotensin II (Ang II) plays a critical role in the development of diabetic cardiomyopathy. Therefore, whether SFN prevents Ang II-induced cardiomyopathy through activation of Nrf2 was examined using wild-type, global deletion of Nrf2 gene (Nrf2-KO) and cardiomyocyte-specific overexpression of Nrf2 gene (Nrf2-TG) mice. Methods and results: Administration of a subpressor dose of Ang II to wild-type mice induced cardiac oxidative stress, inflammation, remodeling and dysfunction, all of which could be prevented by SFN treatment with Nrf2 up-regulation and activation. Nrf2-KO mice are susceptible, and Nrf2-TG mice are resistant, respectively, to Ang II-induced cardiomyopathy. Meanwhile, the ability of SFN to protect against Ang II-induced cardiac damage was lost in Nrf2-KO mice. Up-regulation and activation of Nrf2 by SFN is accompanied by activation of Akt, inhibition of glycogen synthase kinase (GSK)-3β, and accumulation of Fyn in nuclei. In vitro up-regulation of Nrf2 by SFN was abolished and nuclear Fyn accumulation was increased when cardiac cells were exposed to a PI3K inhibitor or GSK-3β-specific activator. Conclusion: These results suggest that Nrf2 plays a central role in the prevention of Ang II-induced cardiomyopathy, and SFN prevents Ang II-induced cardiomyopathy partially via the Akt/GSK-3β/Fyn-mediated Nrf2 activation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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