Sulforaphane prevents angiotensin II-induced cardiomyopathy by activation of Nrf2 via stimulating the Akt/GSK-3ß/Fyn pathway
Xin Y, Bai Y, Jiang X, Zhou S, Wang Y, Wintergerst KA, Cui T, Ji H, Tan Y, Cai L
Redox biology · 147 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Nonprofit
- American Diabetes Association
- Government
- National Natural Science Foundation of China
- University or hospital
- Jilin University
- Government
- National Center for Complementary and Integrative Health
- Government
- NCCIH NIH HHS
- Grants
- National Natural Science Foundation of China (2015225); National Natural Science Foundation of China (81671378); National Natural Science Foundation of China (1-15-BS-018); National Natural Science Foundation of China (81470495); National Natural Science Foundation of China (2015203); National Natural Science Foundation of China (81370318); National Natural Science Foundation of China (81570344); National Center for Complementary and Integrative Health (P01 AT003961); Jilin University (2015225); Jilin University (2015203); Jilin University (81273509); National Natural Science Foundation of China (81300186); National Natural Science Foundation of China (81273509); American Diabetes Association (1–15-BS-018); American Diabetes Association (81273509); National Natural Science Foundation of China (81400281); American Diabetes Association (81370318); National Natural Science Foundation of China (81470061); Jilin University (81570344)
Based on 5 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-01-02 · Redox Biol · vol. 15 · pp. 405–417
- Publisher
- Elsevier BV
- Cited
- 182 citations · more than 98% of similar papers · 6.8× the field average
- Impact
- Top 10% most cited in its field
- References
- 43 works
- Access
- Open access (journal) · CC-BY-NC-ND
- Research areas
- Genomics, phytochemicals, and oxidative stress · Protein Tyrosine Phosphatases · Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- FYN, Sulforaphane, Cardiomyopathy, Angiotensin II, Protein kinase B, Diabetic cardiomyopathy, Chemistry, Activator (genetics), Endocrinology, GSK3B, Internal medicine, Oxidative stress, GSK-3, Cancer research, Phosphorylation, Heart failure, Biology, Medicine, Biochemistry, Gene, Receptor, Proto-oncogene tyrosine-protein kinase Src
- MeSH
- heart, animals, mice, knockout, humans, disease models, animal, isothiocyanates, sulfoxides, angiotensin ii, signal transduction, oxidative stress, male, proto-oncogene proteins c-akt, proto-oncogene proteins c-fyn, nf-e2-related factor 2, phosphatidylinositol 3-kinases, diabetic cardiomyopathies, glycogen synthase kinase 3 beta
10 authors
From CN, US
- Ying XinMinistry of Education of the People's Republic of China; University of Louisville; Jilin University; Wenzhou Medical University
- Yang BaiUniversity of Louisville; Jilin University; First Hospital of Jilin University
- Xin Mei JiangUniversity of Louisville; Jilin University; First Hospital of Jilin University
- Shanshan ZhouUniversity of Louisville; Jilin University; First Hospital of Jilin University
- Yuehui WangJilin University; First Hospital of Jilin University
- Kupper A. WintergerstUniversity of Louisville; Kosair Children's Hospital; Diabetes Care Center; Norton Hospital; University of Louisville Hospital
Abstract
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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