Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress
Li D, Shao R, Wang N, Zhou N, Du K, Shi J, Wang Y, Zhao Z, Ye X, Zhang X, Xu H
Autophagy · 140 citas
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Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
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- Células o muestras de laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Natural Science Foundation of China
- Gobierno
- National Institutes of Health
- Gobierno
- National Institute of Diabetes and Digestive and Kidney Diseases
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Gobierno
- NIDDK NIH HHS
- Gobierno
- NINDS NIH HHS
- Subvenciones
- National Institute of Neurological Disorders and Stroke (R01 NS062792); National Natural Science Foundation of China (31600823); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK115474); National Institutes of Health (DK115474); National Institutes of Health (NS062792)
Según 6 financiadores declarados.
Publicación
- Publicado
- 2020-03-06 · Autophagy · vol. 17 · número 4 · págs. 872–887
- Editorial
- Taylor & Francis
- Citado
- 172 citas · más que el 97% de estudios similares · 5.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 57 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Genomics, phytochemicals, and oxidative stress · Calcium signaling and nucleotide metabolism · Adenosine and Purinergic Signaling
- Palabras clave
- Lysosome, Biology, Oxidative stress, Autophagy, Cell biology, Sulforaphane, TFEB, Biochemistry, Enzyme, Apoptosis
- MeSH
- hela cells, cell nucleus, lysosomes, mitochondria, humans, calcium, reactive oxygen species, isothiocyanates, sulfoxides, calcineurin, transcription, genetic, gene expression regulation, protein transport, oxidative stress, phosphorylation, autophagy, nf-e2-related factor 2, basic helix-loop-helix leucine zipper transcription factors, hek293 cells
11 autores
- Dan Li🇺🇸🇨🇳University of Michigan; Zhejiang University of Technology
- Rong Shao🇨🇳Zhejiang University of Technology
- Na Wang🇺🇸🇨🇳University of Michigan; Zhejiang University of Technology
- Nan Zhou🇺🇸🇨🇳University of Michigan; Zhejiang University of Technology
- Kaili Du🇺🇸🇨🇳University of Michigan; Zhejiang University of Technology
- Jiahui Shi🇨🇳Zhejiang University of Technology
- Yihan Wang🇺🇸🇨🇳University of Michigan; Zhejiang University of Technology
- Zhuangzhuang Zhao🇺🇸🇨🇳University of Michigan; Zhejiang University of Technology
- Xin Ye🇨🇳Zhejiang University of Technology
- Xiaoli Zhang🇺🇸University of Michigan
- Haoxing Xu🇺🇸 · autor de correspondenciaUniversity of Michigan
Resumen
El texto original del estudio, en el idioma en que se publicó.
Oxidative stress underlies a number of pathological conditions, including cancer, neurodegeneration, and aging. Antioxidant-rich foods help maintain cellular redox homeostasis and mitigate oxidative stress, but the underlying mechanisms are not clear. For example, sulforaphane (SFN), an electrophilic compound that is enriched in cruciferous vegetables such as broccoli, is a potent inducer of cellular antioxidant responses. NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2), a transcriptional factor that controls the expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a proposed target of SFN. NFE2L2/NRF2 is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN. SFN induces TFEB nuclear translocation via a Ca2+-dependent but MTOR (mechanistic target of rapamycin kinase)-independent mechanism through a moderate increase in reactive oxygen species (ROS). Activated TFEB then boosts the expression of genes required for autophagosome and lysosome biogenesis, which are known to facilitate the clearance of damaged mitochondria. Notably, TFEB activity is required for SFN-induced protection against both acute oxidant bursts and chronic oxidative stress. Hence, by simultaneously activating macroautophagy/autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases.Abbreviations: ANOVA: analyzes of variance; AREs: antioxidant response elements; Baf-A1: bafilomycin A1; BHA: butylhydroxyanisole; CAT: catechin hydrate; CCCP: carbonyl cyanide m- chlorophenylhydrazone; CLEAR: coordinated lysosomal expression and regulation; DCFH-DA: 2',7'-dichlorofluorescin diacetate; FBS: fetal bovine serum; GFP: green fluorescent protein; HMOX1/HO-1: heme oxygenase 1; KD: knockdown; KEAP1: kelch like ECH associated protein 1; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MCOLN1/TRPML1: mucolipin 1; ML-SA1: mucolipin-specific synthetic agonist 1; ML-SI3: mucolipin-specific synthetic inhibitor 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: nuclear factor: erythroid 2 like 2; NPC: Niemann-Pick type C; PBS: phosphate-buffered saline; PPP2/PP2A: protein phosphatase 2; Q-PCR: real time polymerase chain reaction; ROS: reactive oxygen species; RPS6KB1/S6K1/p70S6K: ribosomal protein S6 kinase B1; SFN: sulforaphane; TFEB: transcription factor EB; WT, wild-type.
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