ArticleAntioxidants & redox signaling2017
The Indirubin Derivative 6-Bromoindirubin-3'-Oxime Activates Proteostatic Modules, Reprograms Cellular Bioenergetic Pathways, and Exerts Antiaging Effects.
Article in Antioxidants & redox signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Dual Inhibition of GSK3 and JAK by BIO Suppresses Osteoblast Differentiation and Mineralization of Human Mesenchymal Cells.Current issues in molecular biology · 2026Article
- Identification of disease-related genes and construction of a gene co-expression database in non-alcoholic fatty liver disease.Frontiers in genetics · 2023Article
- Isolation of an Extract from the Soft Coral Symbiotic MicroorganismCurrent issues in molecular biology · 2021Article
- Differential Dose- and Tissue-Dependent Effects of foxo on Aging, Metabolic and Proteostatic Pathways.Cells · 2021Article
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- Natural Products as Modulators of the Proteostasis Machinery: Implications in Neurodegenerative Diseases.International journal of molecular sciences · 2019Review
- Nrf2, stress and aging.Aging · 2019Article
- Functional wiring of proteostatic and mitostatic modules ensures transient organismal survival during imbalanced mitochondrial dynamics.Redox biology · 2019Article
- Hyperactivation of Nrf2 increases stress tolerance at the cost of aging acceleration due to metabolic deregulation.Aging cell · 2019Article
- Alterations in Organismal Physiology, Impaired Stress Resistance, and Accelerated Aging inOxidative medicine and cellular longevity · 2019Article
- 6-Bromoindirubin-3'-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver.Frontiers in pharmacology · 2019Article
- Nutrigenomics as a tool to study the impact of diet on aging and age-related diseases: theGenes & nutrition · 2019Review
- Indirubin suppresses ovarian cancer cell viabilities through the STAT3 signaling pathway.Drug design, development and therapy · 2018Article
- 6-bromo-indirubin-3'-oxime (6BIO), a Glycogen synthase kinase-3β inhibitor, activates cytoprotective cellular modules and suppresses cellular senescence-mediated biomolecular damage in human fibroblasts.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsOrganismal aging can be delayed by mutations that either activate stress responses or reduce the nutrient-sensing pathway signaling; thus, by using Drosophila melanogaster as an in vivo experimental screening platform, we searched for compounds that modulate these pathways.
resultsWe noted that oral administration of the glycogen synthase kinase 3 (Gsk-3) inhibitor 6-bromoindirubin-3'-oxime (6BIO) in Drosophila flies extended healthy life span. 6BIO is not metabolized in fly tissues, modulated bioenergetic pathways, decreased lipid and glucose tissue load, activated antioxidant and proteostatic modules, and enhanced resistance to stressors. Mechanistically, we found that the effects on the stress-responsive pathways were largely dependent on the activity of the transcription factor nuclear factor erythroid 2-related factor (Nrf-2). Genetic inhibition of Gsk-3 largely phenocopied the 6BIO-mediated effects, while high levels of Gsk-3 expression and/or kinase activity suppressed proteostatic modules and reduced flies' longevity; these effects were partially rescued by 6BIO. Also, 6BIO was found to partially reduce the 3-phosphoinositide-dependent protein kinase-1 (Pdpk1) activity, a major effector of the insulin/insulin-like growth factor-1 cell signaling pathways. INNOVATION: 6BIO exerts the unique property of increasing stress tolerance and in parallel partially suppressing the nutrient-sensing pathway signaling.
conclusionOur findings suggest that the 6BIO scaffold can be used for the development of novel antiaging compounds. Antioxid. Redox Signal. 27, 1027-1047.
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