دورية أكاديمية
Hydralazine Revives Cellular and Ocular Lens Health-Span by Ameliorating the Aging and Oxidative-Dependent Loss of the Nrf2-Activated Cellular Stress Response
| العنوان: | Hydralazine Revives Cellular and Ocular Lens Health-Span by Ameliorating the Aging and Oxidative-Dependent Loss of the Nrf2-Activated Cellular Stress Response |
|---|---|
| المؤلفون: | Bhavana Chhunchha, Eri Kubo, Ronald R. Krueger, Dhirendra P. Singh |
| المصدر: | Antioxidants, Vol 12, Iss 1, p 140 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | aging, oxidative stress, antioxidants, Nrf2, peroxiredoxin 6, hydralazine, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | A major hallmark of aging-associated diseases is the inability to evoke cellular defense responses. Transcriptional protein Nrf2 (nuclear factor erythroid-derived 2-related factor) plays a pivotal role in the oxidative stress response, cellular homeostasis, and health span. Nrf2’s activation has been identified as a therapeutic target to restore antioxidant defense in aging. Here, we demonstrated that FDA-approved drug, hydralazine (Hyd), was a reactivator of the Nrf2/ARE (antioxidant response element) pathway in various ages and types of mouse (m) or human (h) lens epithelial cells (LECs) and mice lenses in-vitro/in-vivo. This led to Hyd-driven abatement of carbonyls, reduced reactive oxygen species (ROS), and reduced 4-HNE/MDA-adducts with cytoprotection, and extended lens healthspan by delaying/preventing lens opacity against aging/oxidative stress. We elucidated that Hyd activated the protective signaling by inducing Nrf2 to traverse from the cytoplasm to the nucleus and potentiated the ARE response by direct interaction of Nrf2 and ARE sequences of the promoter. Loss-of-function study and cotreatment of Hyd and antioxidant, N-acetyl cysteine (NAC) or Peroxiredoxin (Prdx)6, specified that Nrf2/ARE-driven increase in the promoter activity was Hyd-dependent. Our study provides proof-of concept evidence and, thereby, paves the way to repurposing Hyd as a therapeutic agent to delay/prevent aging and oxidative-related disorders. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2076-3921 54115183 |
| Relation: | https://www.mdpi.com/2076-3921/12/1/140; https://doaj.org/toc/2076-3921 |
| DOI: | 10.3390/antiox12010140 |
| URL الوصول: | https://doaj.org/article/ad798a0d5d9a4605bb54115183f3fabf |
| رقم الأكسشن: | edsdoj.798a0d5d9a4605bb54115183f3fabf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20763921 54115183 |
|---|---|
| DOI: | 10.3390/antiox12010140 |