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Author Shinkai, Yasuhiro ♦ Kimura, Tomoki ♦ Itagaki, Ayaka ♦ Yamamoto, Chika ♦ Taguchi, Keiko ♦ Yamamoto, Masayuki ♦ Kumagai, Yoshito ♦ Kaji, Toshiyuki
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANTIOXIDANTS ♦ CADMIUM ♦ CATTLE ♦ CHROMATIN ♦ ECR HEATING ♦ ENDOTHELIUM ♦ GENES ♦ METALLOTHIONEIN ♦ MODULATION ♦ PROMOTERS ♦ THIOLS ♦ TRANSCRIPTION ♦ TRANSCRIPTION FACTORS
Abstract Cadmium is an environmental electrophile that modifies protein reactive thiols such as Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of nuclear factor-erythroid 2-related factor 2 (Nrf2). In the present study, we investigated a role of the Keap1–Nrf2 system in cellular response to cadmium in vascular endothelial cells. Exposure of bovine aortic endothelial cells to cadmium resulted in modification of Keap1 and Nrf2 activation, thereby up-regulating not only its typical downstream proteins but also metallothionein-1/2. Experiments with siRNA-mediated knockdown of Nrf2 or Keap1 supported participation of the Keap1–Nrf2 system in the modulation of metallothionein-1/2 expression. Furthermore, chromatin immunoprecipitation assay showed that Nrf2 was recruited to the antioxidant response element of the promoter region of the bovine metallothionein-2 gene in the presence of cadmium. These results suggest that the transcription factor Nrf2 plays, at least in part, a role in the changes in metallothionein expression mediated by exposure to cadmium. - Highlights: • Role of the Keap1–Nrf2 system in cellular response to cadmium was examined. • We used bovine aortic endothelial cells as a model of the vascular endothelium. • Exposure of cells to cadmium resulted in modification of Keap1 and Nrf2 activation. • Keap1–Nrf2 system participated in the modulation of metallothionein-1/2 expression. • Nrf2 was recruited to the antioxidant response element of MT2 promoter region.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-03-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 295


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