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Quantitative analysis of mRNA expression levels of aldo-keto reductase and short-chain dehydrogenase/reductase isoforms in human livers.
Amai, Keito; Fukami, Tatsuki; Ichida, Hiroyuki; Watanabe, Akiko; Nakano, Masataka; Watanabe, Kengo; Nakajima, Miki.
Afiliación
  • Amai K; Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
  • Fukami T; Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
  • Ichida H; Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
  • Watanabe A; Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd. Tokyo, Japan.
  • Nakano M; Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
  • Watanabe K; Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd. Tokyo, Japan.
  • Nakajima M; Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan. Electronic address: nmiki@p.kanazawa-u.ac.jp.
Drug Metab Pharmacokinet ; 35(6): 539-547, 2020 Dec.
Article en En | MEDLINE | ID: mdl-33036882
The aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase (SDR) superfamilies are responsible for the reduction in compounds containing the aldehyde, ketone, and quinone groups. In humans, 12 AKR isoforms (AKR1A1, AKR1B1, AKR1B10, AKR1B15, AKR1C1, AKR1C2, AKR1C3, AKR1C4, AKR1D1, AKR1E2, AKR7A2, and AKR7A3) and 6 SDR isoforms (CBR1, CBR3, CBR4, HSD11B1, DHRS4, and DCXR) have been found to catalyze the reduction in xenobiotics, but their hepatic expression levels are unclear. The purpose of this study is to determine the absolute mRNA expression levels of these 18 isoforms in the human liver. In 22 human livers, all isoforms, except for AKR1B15, are expressed, and AKR1C2 (on average 1.6 × 106 copy/µg total RNA), AKR1C3 (1.3 × 106), AKR1C1 (1.3 × 106), CBR1 (9.7 × 105), and HSD11B1 (1.1 × 106) are abundant, representing 67% of the total expression of reductases in the liver. The expression levels of AKR1C2, AKR1C3, AKR1C1, CBR1, and HSD11B1 are significantly correlated with each other, except between AKR1C2 and CBR1, suggesting that they might be regulated by common factor(s). In conclusion, this study comprehensively determined the absolute expression of mRNA expression of each AKR and SDR isoform in the human liver.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Aldo-Ceto Reductasas / Deshidrogenasas-Reductasas de Cadena Corta / Hígado Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Aldo-Ceto Reductasas / Deshidrogenasas-Reductasas de Cadena Corta / Hígado Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido