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Toxico-pharmacological perspective of the Nrf2-Keap1 defense system against oxidative stress in kidney diseases
http://hdl.handle.net/2298/27301
http://hdl.handle.net/2298/27301f8d21846-87a9-4dd9-b0cf-7e3ec29603d9
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
BCP-COMMENTARY+SAITO.pdf (575.2 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2013-03-22 | |||||
| タイトル | ||||||
| タイトル | Toxico-pharmacological perspective of the Nrf2-Keap1 defense system against oxidative stress in kidney diseases | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | Nrf2, chronic kidney disease, acute kidney injury, uremic toxins, renal tubules | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Saito, Hideyuki
× Saito, Hideyuki |
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| 別言語の著者 |
齋藤, 秀之
× 齋藤, 秀之 |
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| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Oxidative stress, including the generation of reactive oxygen species (ROS), appears to be responsible for the high incidence of cardiovascular events in patients with chronic kidney disease (CKD), and for the progression of CKD to end-stage renal disease. The processes for oxidative stress include increased generation and decreased elimination of ROS that could be caused by an impaired antioxidant defense system. Nuclear factor-erythroid-2-related factor 2 (Nrf2) helps protect the kidney against oxidative stress by playing a pivotal role in the cooperative induction of genes that encode antioxidant and detoxifying enzymes. Nrf2 is confined to the cytoplasm as an inactive complex bound to a repressor Kelch-like ECH-associated protein 1 (Keap1), which facilitates ubiquitination of Nrf2. Studies using CKD model animals showed that despite stimulated oxidative stress the nuclear Nrf2 level was suppressed, which led to downregulation of the antioxidant enzymes. Hence, deterioration in Nrf2-Keap1 signaling could contribute to the severity of oxidative stress and the progression of CKD. By contrast, acute kidney injury (AKI) induces activation of renal Nrf2. Nrf2 activators or its proteasomal degradation inhibitors enhance nuclear Nrf2 translocation, inducing potential renoprotective actions against CKD and AKI. In both chronic and acute kidney diseases, sulfate-conjugated uremic toxins appear to enhance ROS production when accumulated in renal cells. An intestinal indole adsorbent ameliorates the progression of CKD by decreasing accumulation of indoxyl sulfate. Therapeutic approaches to prevent oxidative stress via activation of the Nrf2-Keap1 signaling and/or suppression of uremic toxin-induced ROS production could be effective strategies for maintaining kidney function. | |||||
| 書誌情報 |
Biochemical Pharmacology 巻 85, 号 7, p. 865-872, 発行年 2013-04-01 |
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| ISSN | ||||||
| 収録物識別子 | 00062952 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 関連識別子 | 10.1016/j.bcp.2013.01.006 | |||||
| 権利 | ||||||
| 権利情報 | © 2013 Elsevier Inc. | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 形態 | ||||||
| 値 | 575185 bytes | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 494.93 | |||||
| 出版者 | ||||||
| 出版者 | Elsevier Inc. | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 論文(Article) | |||||
| 資源タイプ・ローカル | ||||||
| 値 | 雑誌掲載論文 | |||||
| 資源タイプ・NII | ||||||
| 値 | Journal Article | |||||
| 資源タイプ・DCMI | ||||||
| 値 | text | |||||
| 資源タイプ・ローカル表示コード | ||||||
| 値 | 01 | |||||
| URL | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | http://www.sciencedirect.com/science/article/pii/S0006295213000439 | |||||
