Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27
Gan N, Wu YC, Brunet M, Garrido C, Chung FL, Dai C, Mi L
The Journal of biological chemistry · 103 citations
Review labels
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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
- Government
- U.S. Environmental Protection Agency
- University or hospital
- Northwestern University
- University or hospital
- University of Minnesota
- Government
- Institut National de la Santé et de la Recherche Médicale
- University or hospital
- Universitair Medisch Centrum Groningen
- University or hospital
- Universität zu Köln
- Government
- National Institutes of Health
- Government
- National Cancer Institute
- Government
- NCI NIH HHS
- Grants
- National Cancer Institute (R01 CA100853); National Cancer Institute (CA100853); National Institutes of Health (CA100853)
Based on 9 listed funder(s).
Publication
- Published
- 2010-09-11 · J Biol Chem · vol. 285 · issue 46 · pp. 35528–35536
- Publisher
- Elsevier BV
- Cited
- 141 citations · more than 92% of similar papers · 3.2× the field average
- Impact
- Top 10% most cited in its field
- References
- 49 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Heat shock proteins research · Selenium in Biological Systems
- Keywords
- Sulforaphane, Hsp27, Proteasome, Heat shock protein, Cell biology, KEAP1, Cruciferous vegetables, Cytotoxicity, Heat shock, Chemistry, Heat shock factor, Hsp70, Biology, Biochemistry, Transcription factor, Cancer, In vitro, Genetics
- MeSH
- cos cells, cell line, tumor, hela cells, animals, humans, thiocyanates, isothiocyanates, sulfoxides, proteasome endopeptidase complex, leupeptins, dna-binding proteins, transcription factors, anticarcinogenic agents, cysteine proteinase inhibitors, immunoblotting, reverse transcriptase polymerase chain reaction, protein biosynthesis, rna interference, up-regulation, enzyme activation, heat-shock response, dose-response relationship, drug, hot temperature, hsp27 heat-shock proteins, proteasome inhibitors, heat shock transcription factors, chlorocebus aethiops
7 authors
From US, CN, FR
- Nanqin GanGeorgetown University; Chinese Academy of Sciences; Georgetown University Medical Center; Institute of Hydrobiology
- Yu‐Chieh WuGeorgetown University; Georgetown University Medical Center
- Mathilde BrunetInserm
- Carmen Rosa GarridoInserm
- Fung‐Lung ChungGeorgetown University; Georgetown University Medical Center
- Chengkai DaiJackson Laboratory
Abstract
It is conceivable that stimulating proteasome activity for rapid removal of misfolded and oxidized proteins is a promising strategy to prevent and alleviate aging-related diseases. Sulforaphane (SFN), an effective cancer preventive agent derived from cruciferous vegetables, has been shown to enhance proteasome activities in mammalian cells and to reduce the level of oxidized proteins and amyloid β-induced cytotoxicity. Here, we report that SFN activates heat shock transcription factor 1-mediated heat shock response. Specifically, SFN-induced expression of heat shock protein 27 (Hsp27) underlies SFN-stimulated proteasome activity. SFN-induced proteasome activity was significantly enhanced in Hsp27-overexpressing cells but absent in Hsp27-silenced cells. The role of Hsp27 in regulating proteasome activity was further confirmed in isogenic REG cells, in which SFN-induced proteasome activation was only observed in cells stably overexpressing Hsp27, but not in the Hsp27-free parental cells. Finally, we demonstrated that phosphorylation of Hsp27 is irrelevant to SFN-induced proteasome activation. This study provides a novel mechanism underlying SFN-induced proteasome activity. This is the first report to show that heat shock response by SFN, in addition to the antioxidant response mediated by the Keap1-Nrf2 pathway, may contribute to cytoprotection.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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