Sulforaphane enhances progerin clearance in Hutchinson-Gilford progeria fibroblasts
Gabriel D, Roedl D, Gordon LB, Djabali K
Aging cell · 87 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Progeria Research Foundation
- Nonprofit
- Alexander von Humboldt-Stiftung
- Grants
- Alexander von Humboldt-Stiftung (5090371); Progeria Research Foundation (2012-44)
Based on 2 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2014-12-16 · Aging Cell · vol. 14 · issue 1 · pp. 78–91
- Publisher
- Wiley
- Cited
- 116 citations · more than 94% of similar papers · 3.8× the field average
- Impact
- Top 10% most cited in its field
- References
- 47 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Nuclear Structure and Function · Ubiquitin and proteasome pathways · Retinoids in leukemia and cellular processes
- Keywords
- Progeria, LMNA, Biology, Proteasome, Sulforaphane, Premature aging, Autophagy, Cell biology, Phenotype, Farnesyltransferase, Molecular biology, Cancer research, Biochemistry, Genetics, Gene, Apoptosis, Prenylation
- MeSH
- cell line, cell nucleus, fibroblasts, humans, progeria, dna damage, isothiocyanates, sulfoxides, proteasome endopeptidase complex, lamin type a, proteome, enzyme inhibitors, electrophoresis, gel, two-dimensional, proteomics, drug synergism, phenotype, mass spectrometry, proteolysis
4 authors
From DE, US
- Diana GabrielTechnical University of Munich
- Daniela RoedlTechnical University of Munich
- Leslie B. GordonBoston Children's Hospital; Harvard University; Brown University; Hasbro Children's Hospital; Boston Children's Museum
- Karima Djabali · correspondingTechnical University of Munich
Abstract
Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare multisystem childhood premature aging disorder linked to mutations in the LMNA gene. The most common HGPS mutation is found at position G608G within exon 11 of the LMNA gene. This mutation results in the deletion of 50 amino acids at the carboxyl-terminal tail of prelamin A, and the truncated protein is called progerin. Progerin only undergoes a subset of the normal post-translational modifications and remains permanently farnesylated. Several attempts to rescue the normal cellular phenotype with farnesyltransferase inhibitors (FTIs) and other compounds have resulted in partial cellular recovery. Using proteomics, we report here that progerin induces changes in the composition of the HGPS nuclear proteome, including alterations to several components of the protein degradation pathways. Consequently, proteasome activity and autophagy are impaired in HGPS cells. To restore protein clearance in HGPS cells, we treated HGPS cultures with sulforaphane (SFN), an antioxidant derived from cruciferous vegetables. We determined that SFN stimulates proteasome activity and autophagy in normal and HGPS fibroblast cultures. Specifically, SFN enhances progerin clearance by autophagy and reverses the phenotypic changes that are the hallmarks of HGPS. Therefore, SFN is a promising therapeutic avenue for children with HGPS.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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