Artikel: Keap1 modification and nuclear accumulation in response to S-nitrosocysteine.
Free radical biology & medicine
2007 Band 44, Heft 4, Seite(n) 692–698
Abstract: Keap1 is a key regulator of the Nrf2 transcription factor, which transactivates the antioxidant response element (ARE) and upregulates numerous proteins involved in antioxidant defense. Under basal conditions, Keap1 targets Nrf2 for ubiquitination and ... ...
Abstract | Keap1 is a key regulator of the Nrf2 transcription factor, which transactivates the antioxidant response element (ARE) and upregulates numerous proteins involved in antioxidant defense. Under basal conditions, Keap1 targets Nrf2 for ubiquitination and proteolytic degradation and as such is responsible for the rapid turnover of Nrf2. In response to oxidants and electrophiles, Nrf2 is stabilized and accumulates in the nucleus. The mechanism for this effect has been proposed to involve thiol-dependent modulation of Keap1 leading to loss of its ability to negatively regulate Nrf2. We have previously shown that nitric oxide and S-nitrosothiols cause nuclear accumulation of Nrf2 and upregulation of the ARE-regulated gene HO-1. Here we show that nitric oxide and S-nitrosocysteine (CSNO) cause time- and dose-dependent Keap1 thiol modification. These studies were carried out in HEK293 cells and in HEK293 cells overexpressing hemagglutinin-tagged Keap1. Furthermore we demonstrate that in response to CSNO Keap1 accumulates in the nucleus with a time course similar to that of Nrf2. |
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Mesh-Begriff(e) | Active Transport, Cell Nucleus ; Cell Nucleus/metabolism ; Cells, Cultured ; Cysteine/analogs & derivatives ; Cysteine/pharmacology ; Dithiothreitol/pharmacology ; Dose-Response Relationship, Drug ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2/metabolism ; S-Nitrosothiols/pharmacology ; Spermine/analogs & derivatives ; Spermine/pharmacology |
Chemische Substanzen | Intracellular Signaling Peptides and Proteins ; KEAP1 protein, human ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; S-Nitrosothiols ; spermine nitric oxide complex (136587-13-8) ; Spermine (2FZ7Y3VOQX) ; S-nitrosocysteine (926P2322P4) ; Cysteine (K848JZ4886) ; Dithiothreitol (T8ID5YZU6Y) |
Sprache | Englisch |
Erscheinungsdatum | 2007-11-13 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural |
ZDB-ID | 807032-5 |
ISSN | 1873-4596 ; 0891-5849 |
ISSN (online) | 1873-4596 |
ISSN | 0891-5849 |
DOI | 10.1016/j.freeradbiomed.2007.10.055 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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