RESUMEN
Resveratrol is a promising chemical agent that treats multiple aging-related diseases and improves life span. While reactive oxygen species undoubtedly play ubiquitous roles in the aging process and resveratrol has been shown to be an effective antioxidant, the mechanism through which resveratrol acts against oxidative stress remains unknown. Here we show that resveratrol activates SIRT2 to deacetylate Prx1, leading to an increased H2O2 reduction activity and a decreased cellular H2O2 concentration. Knockdown of SIRT2 or Prx1 by RNA interference abrogates resveratrol's ability to reduce the H2O2 level in HepG2 cells. Using purified SIRT2 and a Prx1 mutant harboring acetyllysine at position 27 (Prx1-27AcK), we show that resveratrol enhances SIRT2's activity to deacetylate Prx1-27AcK, resulting in a significantly increased H2O2 reducing activity. Thus, SIRT2 and Prx1 are targets for modulating intracellular redox status in the therapeutic strategies for the treatment of aging-related disorders.
Asunto(s)
Antioxidantes/farmacología , Proteínas de Homeodominio/metabolismo , Sirtuina 2/metabolismo , Estilbenos/farmacología , Antioxidantes/química , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Proteínas de Homeodominio/genética , Humanos , Peróxido de Hidrógeno , Resveratrol , Sirtuina 2/genética , Estilbenos/químicaAsunto(s)
Aminoácidos/química , Quelantes/química , Proteínas Luminiscentes/química , Alanina/química , Alanina/metabolismo , Aminoácidos/metabolismo , Dominio Catalítico , Citrobacter freundii/enzimología , Transferencia Resonante de Energía de Fluorescencia , Hidroxiquinolinas/química , Proteínas Luminiscentes/metabolismo , Metales/química , Mutación , Espectrofotometría Ultravioleta , Tirosina Fenol-Liasa/química , Tirosina Fenol-Liasa/genética , Tirosina Fenol-Liasa/metabolismoAsunto(s)
Cisteína/metabolismo , Tirosina/metabolismo , Animales , Dominio Catalítico , Cisteína/química , Cisteína-Dioxigenasa/metabolismo , Citocromos a1/química , Citocromos a1/metabolismo , Citocromos c1/química , Citocromos c1/metabolismo , Galactosa Oxidasa/metabolismo , Mutagénesis Sitio-Dirigida , Mioglobina/genética , Mioglobina/metabolismo , Nitrato Reductasas/química , Nitrato Reductasas/metabolismo , Oxidación-Reducción , Sulfito Reductasa (Ferredoxina)/metabolismo , Tirosina/análogos & derivados , BallenasRESUMEN
Easy-to-use dipstick tests for lead have been developed by immobilizing nanoparticle-DNAzyme conjugates on lateral flow devices and their application for detecting lead in paints is demonstrated.