Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress
Kubo E, Chhunchha B, Singh P, Sasaki H, Singh DP
Scientific reports · 190 citas
Etiquetas de revisión
Solo mecanismosDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Research to Prevent Blindness
- Gobierno
- National Institutes of Health
- Gobierno
- National Eye Institute
- Gobierno
- NEI NIH HHS
- Subvenciones
- National Eye Institute (EY024589); National Eye Institute (R01 EY024589); National Institutes of Health (EY024589)
Según 4 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2017-10-20 · Sci Rep · vol. 7 · número 1 · pág. 14130
- Editorial
- Nature Portfolio
- Citado
- 231 citas · más que el 98% de estudios similares · 6.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 93 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Genomics, phytochemicals, and oxidative stress · Selenium in Biological Systems · Redox biology and oxidative stress
- Palabras clave
- Sulforaphane, Oxidative stress, Gene knockdown, Cytoprotection, Activator (genetics), Chemistry, Transcription factor, DNA damage, Catalase, Cell biology, Antioxidant, Molecular biology, Electrophoretic mobility shift assay, Biology, Apoptosis, Biochemistry, Gene, DNA
- MeSH
- cell nucleus, animals, humans, rats, rats, sprague-dawley, isothiocyanates, sulfoxides, antioxidants, transcription, genetic, gene expression regulation, up-regulation, response elements, active transport, cell nucleus, oxidative stress, aging, dose-response relationship, drug, time factors, adolescent, adult, aged, middle aged, nf-e2-related factor 2, peroxiredoxin vi, promoter regions, genetic, young adult
5 autores
- Eri Kubo🇯🇵 · autor de correspondenciaKanazawa University; Kanazawa Medical University; Kanazawa Medical Center
- Bhavana Chhunchha🇺🇸University of Nebraska Medical Center
- Prerna Singh🇺🇸University of Nebraska Medical Center
- Hiroshi Sasaki🇯🇵Kanazawa Medical University
- Dhirendra Pratap Singh🇺🇸 · autor de correspondenciaNebraska Medical Center; University of Nebraska Medical Center
Resumen
El texto original del estudio, en el idioma en que se publicó.
Upon oxidative stress and aging, Nrf2 (NFE2-related factor2) triggers antioxidant defense genes to defends against homeostatic failure. Using human(h) or rat(r) lens epithelial cells (LECs) and aging human lenses, we showed that a progressive increase in oxidative load during aging was linked to a decline in Prdx6 expression. DNA binding experiments using gel-shift and ChIP assays demonstrated a progressive reduction in Nrf2/ARE binding (-357/-349) of Prdx6 promoter. The promoter (-918) with ARE showed a marked reduction in young vs aged hLECs, which was directly correlated to decreased Nrf2/ARE binding. A Nrf2 activator, Sulforaphane (SFN), augmented Prdx6, catalase and GSTπ expression in dose-dependent fashion, and halted Nrf2 dysregulation of these antioxidants. SFN reinforced Nrf2/DNA binding and increased promoter activities by enhancing expression and facilitating Nrf2 translocalization in nucleus. Conversely, promoter mutated at ARE site did not respond to SFN, validating the SFN-mediated restoration of Nrf2/ARE signaling. Furthermore, SFN rescued cells from UVB-induced toxicity in dose-dependent fashion, which was consistent with SFN's dose-dependent activation of Nrf2/ARE interaction. Importantly, knockdown of Prdx6 revealed that Prdx6 expression was prerequisite for SFN-mediated cytoprotection. Collectively, our results suggest that loss of Prdx6 caused by dysregulation of ARE/Nrf2 can be attenuated through a SFN, to combat diseases associated with aging.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.