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Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27
Gan, Nanqin; Wu, Yu-Chieh; Brunet, Mathilde; Garrido, Carmen; Chung, Fung-Lung; Dai, Chengkai; Mi, Lixin; Mi, LX, Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd,LL 129,Box 571465, Washington, DC 20057 USA
2010
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
Volume285Issue:46Pages:35528-35536
AbstractIt 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 beta-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.
KeywordDna-binding Activity Alpha-b-crystallin Transcription Factor Increased Expression 26s Proteasome Cancer Cells Redox State Protein Degradation Induction
Department[Mi, Lixin] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA; [Gan, Nanqin] Chinese Acad Sci, Inst Hydrobiol, Beijing 100864, Peoples R China; [Brunet, Mathilde; Garrido, Carmen] INSERM, Fac Med & Pharm, UMR 866, F-21049 Dijon, France; [Dai, Chengkai] Jackson Lab, Bar Harbor, ME 04609 USA
Subject AreaBiochemistry & Molecular Biology
Funding OrganizationNational Institutes of Health through the National Cancer Institute [CA100853] ; National Institutes of Health through the National Cancer Institute [CA100853] ; National Institutes of Health through the National Cancer Institute [CA100853] ; National Institutes of Health through the National Cancer Institute [CA100853]
Indexed BySCI
WOS IDWOS:000283845300031
Funding OrganizationNational Institutes of Health through the National Cancer Institute [CA100853] ; National Institutes of Health through the National Cancer Institute [CA100853] ; National Institutes of Health through the National Cancer Institute [CA100853] ; National Institutes of Health through the National Cancer Institute [CA100853]
Citation statistics
Cited Times:73[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/13759
Collection藻类生物学及应用研究中心_期刊论文
Corresponding AuthorMi, LX, Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd,LL 129,Box 571465, Washington, DC 20057 USA
Recommended Citation
GB/T 7714
Gan, Nanqin,Wu, Yu-Chieh,Brunet, Mathilde,et al. Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2010,285(46):35528-35536.
APA Gan, Nanqin.,Wu, Yu-Chieh.,Brunet, Mathilde.,Garrido, Carmen.,Chung, Fung-Lung.,...&Mi, LX, Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd,LL 129,Box 571465, Washington, DC 20057 USA.(2010).Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27.JOURNAL OF BIOLOGICAL CHEMISTRY,285(46),35528-35536.
MLA Gan, Nanqin,et al."Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27".JOURNAL OF BIOLOGICAL CHEMISTRY 285.46(2010):35528-35536.
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