Antioxidants Enhance Mammalian Proteasome Expression through the Keap1-Nrf2 Signaling Pathway
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- Mi-Kyoung Kwak
- Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205
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- Nobunao Wakabayashi
- Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205
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- Jennifer L. Greenlaw
- Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205
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- Masayuki Yamamoto
- Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tennoudai, Tsukuba 305-8577, Japan
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- Thomas W. Kensler
- Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205
説明
Proteasomes degrade damaged proteins formed during oxidative stress, thereby promoting cell survival. Neurodegenerative and other age-related disorders are associated with reduced proteasome activity. We show herein that expression of most subunits of 20S and 19S proteasomes, which collectively assemble the 26S proteasome, was enhanced up to threefold in livers of mice following treatment with dithiolethiones, which act as indirect antioxidants. Subunit protein levels and proteasome activity were coordinately increased. No induction was seen in mice where the transcription factor Nrf2 was disrupted. Promoter activity of the PSMB5 subunit of the 20S proteasome increased with either Nrf2 overexpression or treatment with antioxidants in mouse embryonic fibroblasts. Tandem antioxidant response elements in the proximal promoter of PSMB5 that controlled these responses were identified. We propose that induction of the 26S proteasome through the Nrf2 pathway represents an important indirect action of these antioxidants that can contribute to their protective effects against chronic diseases.
収録刊行物
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- Molecular and Cellular Biology
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Molecular and Cellular Biology 23 (23), 8786-8794, 2003-12-01
Informa UK Limited
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キーワード
- Proteasome Endopeptidase Complex
- NF-E2-Related Factor 2
- Gene Expression
- Thiophenes
- In Vitro Techniques
- Antioxidants
- Mice
- Multienzyme Complexes
- Animals
- Promoter Regions, Genetic
- Adaptor Proteins, Signal Transducing
- Oligonucleotide Array Sequence Analysis
- Mice, Knockout
- Kelch-Like ECH-Associated Protein 1
- Base Sequence
- Thiones
- DNA
- DNA-Binding Proteins
- Cysteine Endopeptidases
- Cytoskeletal Proteins
- Liver
- Trans-Activators
- Carrier Proteins
- Signal Transduction
詳細情報 詳細情報について
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- CRID
- 1362825893907514624
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- NII論文ID
- 30021003033
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- ISSN
- 10985549
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- PubMed
- 14612418
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- データソース種別
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- Crossref
- CiNii Articles
- OpenAIRE