Elucidation of defense mechanism against carbonyl stress by reductases for carbonyl compounds

• Project/Area Number: 19890180
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: ENDO Satoshi Gifu Pharmaceutical University, 薬学部, 助手 (60433207)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,622,000 (Direct Cost: ¥2,280,000、Indirect Cost: ¥342,000); Fiscal Year 2008: ¥1,482,000 (Direct Cost: ¥1,140,000、Indirect Cost: ¥342,000); Fiscal Year 2007: ¥1,140,000 (Direct Cost: ¥1,140,000)
• Keywords: カルボニル還元酵素 / アルドーケト還元酵素 / カルボニルストレス / 酸化ストレス / 9,10-phenanthrenequinone / アルドケト還元酵素 / 構造機能相関

Research Abstract

本研究では、カルボニルストレス防御機構の一つとして反応性カルボニル化合物を減少させる酵素系に着目し、AKR1C15、カルボニル還元酵素4 などのカルボニル化合物還元代謝酵素の性状を明らかにした。その結果、これら酵素は反応性アルデヒドをただ効率よく代謝するだけでなく、これら化合物によって発現誘導されることで、さらに効果的に生体を防御していることが明らかとなった。またこれら酵素における基質特異性はオーバーラップするものの、局在性、触媒活性や発現誘導機構は異なり、細胞小器官別の酸化ストレスに起因する疾病の予防または治療における標的タンパクとなりえる可能性も示唆された。

Research Products

• [Journal Article] Characterization of a rat NADPH-dependent aldo-keto reductase (AKR1B13) induced by oxidative stress (2009)
  • Author(s): Satoshi Endo, Toshiyuki Matsunaga, Hiroaki Mamiya, Akira Hara, Yukio Kitade, Kazuo Tajima, Ossama El-Kabbani
  • Journal Title: Chem. Biol. Interact 176 Pages: 151-157
  • Peer Reviewed
• [Journal Article] Characterization of a rat NADPH-dependent aldo-keto reductase (AKR1B13) induced by oxidative stress. (2009)
  • Author(s): Satoshi Endo
  • Journal Title: Chem. Biol. Interact. 176 Pages: 151-157
  • Peer Reviewed
• [Journal Article] Human carbonyl reductase 4 is a mitochondrial NADPH-dependent quinone reductase (2008)
  • Author(s): Satoshi Endo, Toshiyuki Matsunaga, Yukio Kitade, Satoshi Ohno, Kazuo Tajima, Ossama El-Kabbani and Akira Hara
  • Journal Title: Biochem. Biophys. Res. Commun 377 Pages: 1326-1330
  • Peer Reviewed
• [Journal Article] Characterization of human DHRS4: An inducible short-chain dehydrogenase/reductase enzyme with 3beta-hydroxysteroid dehydrogenase activity (2008)
  • Author(s): Toshiyuki Matsunaga, Satoshi Endo, Satoshi Maeda , Shuhei Ishikura, Kazuo Tajima, Nobutada Tanaka, Kazuo TNakamura, Yorishige Imamura, and Akira Hara
  • Journal Title: Arch. Biochem. Biophys 477 Pages: 339-347
  • Peer Reviewed
• [Journal Article] Characterization of human DHRS4 : An inducible short-chain dehydrogenase/reductase enzyme with 3beta-hydroxyste roid dehydrogenase activity. (2008)
  • Author(s): Toshiyuki Matsunaga
  • Journal Title: Arch. Biochem. Biophys. 477 Pages: 339-347
  • Peer Reviewed
• [Journal Article] Human carbonyl reductase 4 is a mitochondrial NADPH-dependent quinone reductase. (2008)
  • Author(s): Satoshi Endo
  • Journal Title: Biochem. Biophys. Res. Commun. 377 Pages: 1326-1330
  • Peer Reviewed
• [Journal Article] Characterization of rat and mouse NAD+-dependent 3alpha/17beta/20alpha-hydroxysteroid dehydrogenases and identification of substrate specificity determinants by site-directed mutagenesis (2007)
  • Author(s): Satoshi Endo, Masaharu Sanai, Kenji Horie, Toshiyuki Matsunaga, Syuhei Ishikura, KazuoTajima, Ossama El-Kabbani, and Akira Hara
  • Journal Title: Arch. Biochem. Biophys 467 Pages: 76-86
  • Peer Reviewed
• [Journal Article] Enzymatic characteristics of an aldo-keto reductase family protein(AKR1C15) and its localization in rat tissues (2007)
  • Author(s): Satoshi Endo, Toshiyuki Matsunaga, Kenji Horie, Kazuo Tajima, Yasuo Bunai, Vincenzo Carbone, Ossama El-Kabbani, Akira Hara
  • Journal Title: Arch. Biochem. Biophys 465 Pages: 136-147
  • Peer Reviewed
• [Journal Article] Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): A member of the aldo-keto reductase family highly expressed in kidney cytosol (2007)
  • Author(s): Masaharu Sanai, Satoshi Endo, Toshiyuki Matsunaga, Shuhei Ishikura, Kazuo Tajima, Ossama El-Kabbani and Akira Hara
  • Journal Title: Arch. Biochem. Biophys 464 Pages: 122-129
  • Peer Reviewed
• [Journal Article] Rat NAD(+)-dependent 3alpha-hydroxysteroid dehydrogenase(AKR1C17): A member of the aldo-keto reductase family highly expressed in kidney cytosol. (2007)
  • Author(s): Masaharu Sanai
  • Journal Title: Arch. Biochem. Biophys. 464 Pages: 122-129
  • Peer Reviewed
• [Journal Article] Enzymatic Characteristics of an Aldo-Keto Reductase Family Protein(AKR1C15)and its Localization in Rat Tissues (2007)
  • Author(s): Satoshi Endo
  • Journal Title: Arch. Biochem. Biophys. 465 Pages: 136-147
  • Peer Reviewed
• [Journal Article] Characterization of rat and mouse NAD+-dependent 3α/17β/20α-hydroxysteroid dehydrogenases and identification of substrate specificity determinants by site-directed mutagenesis (2007)
  • Author(s): Satoshi Endo
  • Journal Title: Arch. Biochem. Biophys. 467 Pages: 76-86
  • Peer Reviewed
• [Presentation] Characterization of a rat aldo-keto reductase (AKR1B13) up-regulated by oxidative stress (2008)
  • Author(s): Satoshi Endo, Toshiyuki Matsunaga, Hiroaki Mamiya, Akira Hara, Kazuo Tajima, Yukio Kitade, Ossama El-Kabbani
  • Organizer: ENZYMOLOGY AND MOLECULAR BIOLOGY OF CARBONYL METABOLISM FOURTEENTH INTERNATIONAL MEETING
  • Place of Presentation: KRANJSKA GORA, SLOVENIA JULY
  • Year and Date: 2008-07-11
• [Presentation] ヒトの誘導性SDR ファミリータンパク質(DHRS4)の性状 (2008)
  • Author(s): 前田 哲志、遠藤 智史、松永 俊之、原明、田中 信忠、中村 和郎、田島 和男
  • Organizer: 第72 回日本生化学会中部支部例会
  • Place of Presentation: 岐阜
  • Year and Date: 2008-05-24
• [Presentation] ヒトの誘導性SDRファミリータンパク質(DHRS4)の性状 (2008)
  • Author(s): 前田 哲志
  • Organizer: 第72回日本生化学会中部支部例会
  • Place of Presentation: 岐阜大学 医学部記念会館 (岐阜県)
  • Year and Date: 2008-05-24
• [Presentation] Characterization of a rat aldo-keto reductase (AKR1B13) up-regulated by oxidative stress (2008)
  • Author(s): Satoshi Endo
  • Organizer: ENZYMOLOGY AND MOLECULAR BIOLOGY OF CARBONYL METABOLISM 14th INTERNATIONAL MEETING
  • Place of Presentation: KRANTSKA GORA, SLOVENIA
• [Presentation] Identification of substrate specificity determinants of rodent NAD+-dependent 3a/17b/20a-hydroxysteroid dehydrogenases by site-directed mutagenesis (2007)
  • Author(s): Satoshi Endo, Toshiyuki Matsunaga, Kazuo Tajima, and Akira Hara
  • Organizer: 第80 回 日本生化学会大会 第30 回 日本分子生物学会年会 合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Identification of substrate specificity determinants of rodent NAD+-dependent 3α/17β/20α-hydroxysteroid dehydrogenases by site-directed mutagenesis (2007)
  • Author(s): 遠藤智史
  • Organizer: 第80回 日本生化学会大会 第30回 日本分子生物学会年会 合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11