Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27

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	Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27
	Gan, Nanqin 2; Wu, Yu-Chieh ; Brunet, Mathilde 3; Garrido, Carmen 3; Chung, Fung-Lung ; Dai, Chengkai 4; Mi, Lixin 1
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2010-11-12
卷号	285 期号:46 页码:35528-35536
关键词	DNA-BINDING ACTIVITY ALPHA-B-CRYSTALLIN TRANSCRIPTION FACTOR INCREASED EXPRESSION 26S PROTEASOME CANCER CELLS REDOX STATE PROTEIN DEGRADATION INDUCTION
ISSN号	0021-9258
通讯作者	Mi, LX, Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd,LL 129,Box 571465, Washington, DC 20057 USA
中文摘要	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 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.
英文摘要	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 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.
学科主题	Biochemistry & Molecular Biology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemistry & Molecular Biology
研究领域[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	DNA-BINDING ACTIVITY ; ALPHA-B-CRYSTALLIN ; TRANSCRIPTION FACTOR ; INCREASED EXPRESSION ; 26S PROTEASOME ; CANCER CELLS ; REDOX STATE ; PROTEIN ; DEGRADATION ; INDUCTION
收录类别	SCI
资助信息	National Institutes of Health through the National Cancer Institute [CA100853]
语种	英语
WOS记录号	WOS:000283845300031
公开日期	2010-12-23
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/13759]
专题	水生生物研究所_藻类生物学及应用研究中心_期刊论文
作者单位	1.Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA 2.Chinese Acad Sci, Inst Hydrobiol, Beijing 100864, Peoples R China 3.INSERM, Fac Med & Pharm, UMR 866, F-21049 Dijon, France 4.Jackson Lab, Bar Harbor, ME 04609 USA
推荐引用方式 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, Lixin.(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.