Studies on the physiological role of Prx4 in oxidative protein folding

• Project/Area Number: 25870075
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry; General medical chemistry
• Research Institution: Kyoto Prefectural University of Medicine (2015-2016); Yamagata University (2013-2014)
• Principal Investigator: Kurahashi Toshihiro 京都府立医科大学, 医学(系)研究科(研究院), 講師 (00596570)
• Research Collaborator: FUJII Junichi 山形大学, 大学院医学研究科, 教授 (00222258) ; TAKAO Toshifumi 大阪大学, 蛋白質研究所, 教授 (10197048)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ペルオキシレドキシン / Prx4 / 小胞体 / 蛋白質の酸化的折畳み / 酸化ストレス

Outline of Final Research Achievements

To elucidate the physiological roles of Prx4, we have analyzed the cultured cells overexpressed Prx4 and Prx4-knockout mice, and obtained following results. (1) We have identified some proteins which might interact with Prx4 or Prx4t. (2) Prx4 might localize to platelet membrane, which suggests Prx4 might be involved in redox remodeling of membrane proteins. (3) We have established Prx4;SOD1 double knockout mice to elucidate roles of Prx4 under oxidative stress in vivo. The double knockout mice had serious hepatic disorder from infant, suggesting pivotal roles of Prx4 in protection against oxidative injury. (4) Overexpressed Prx4t localized in cytoplasm mainly and expressed antioxidant activity in cultured cells.

Research Products

• [Journal Article] Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy. (2016)
  • Author(s): Kurahashi T, Lee J, Nabeshima A, Homma T, Kang ES, Saito Y, Yamada S, Nakayama T, Yamada K, Miyata S, Fujii J.
  • Journal Title: Arch Biochem Biophys Volume: 604 Pages: 36-46
  • DOI: 10.1016/j.abb.2016.06.004
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase. (2016)
  • Author(s): Otsuki N, Homma T, Fujiwara H, Kaneko K, Hozumi Y, Shichiri M, Takashima M, Ito J, Konno T, Kurahashi T, Yoshida Y, Goto K, Fujii S, Fujii J.
  • Journal Title: Regul Toxicol Pharmacol Volume: 79 Pages: 83-90
  • DOI: 10.1016/j.yrtph.2016.05.007
  • Peer Reviewed
• [Journal Article] The SOD1 transgene expressed in erythroid cells alleviates fatal phenotype in congenic NZB/NZW-F1 mice. (2016)
  • Author(s): Otsuki N, Konno T, Kurahashi T, Suzuki S, Lee J, Okada F, Iuchi Y, Homma T, Fujii J.
  • Journal Title: Free Radic Res Volume: 50 Issue: 7 Pages: 793-800
  • DOI: 10.1080/10715762.2016.1178388
  • Peer Reviewed
• [Journal Article] Overexpression of Peroxiredoxin 4 Induces Adaptive Intestinal Lipid Metabolism Associated with Suppressive Nonalcoholic Steatohepatitis in a Dietary Mouse Model. (2016)
  • Author(s): Aya Nawata, Hirotsugu Noguchi, Yuichi Mazaki, Toshihiro Kurahashi, Atsunori Nabeshima, Ke-Yong Wang, Satoshi Kimura, Hidetaka Uramoto, Kimitoshi Kohno, Hatsumi Taniguchi, Yoshiya Tanaka, Junichi Fujii, Yasuyuki Sasaguri Toshiyuki Nakayama, and Sohsuke Yamada.
  • Journal Title: PLoS One Volume: e0152549 Issue: 4 Pages: e0152549-e0152549
  • DOI: 10.1371/journal.pone.0152549
  • Peer Reviewed / Open Access
• [Journal Article] An SOD1 deficiency enhances lipid droplet accumulation in the fasted mouse liver by aborting lipophagy (2015)
  • Author(s): Toshihiro Kurahashi, Shinji Hamashima, Takaya Shirato, Jaeyong Lee, Takujiro Homma, Eun Sil Kang, Junichi Fujii.
  • Journal Title: Biochem Biophys Res Commun Volume: 467 Issue: 4 Pages: 866-871
  • DOI: 10.1016/j.bbrc.2015.10.052
  • Peer Reviewed
• [Journal Article] SOD1 deficiency decreases proteasomal function, leading to the accumulation of ubiquitinated proteins in erythrocytes. (2015)
  • Author(s): Takujiro Homma, Toshihiro Kurahashi, Jaeyong Lee, Eun Sil Kang and Junichi Fujii
  • Journal Title: Arch Biochem Biophys Volume: 583 Pages: 65-72
  • DOI: 10.1016/j.abb.2015.07.023
  • Peer Reviewed
• [Journal Article] Oxidative stress triggers lipid droplet accumulation in primary cultured hepatocytes by activating fatty acid synthesis. (2015)
  • Author(s): Jaeyong Lee, Takujiro Homma, Toshihiro Kurahashi, Eun Sil Kang, andJunichi Fujii.
  • Journal Title: Biochem Biophys Res Commun Volume: 464 Issue: 1 Pages: 229-235
  • DOI: 10.1016/j.bbrc.2015.06.121
  • Peer Reviewed
• [Journal Article] SOD1 deficiency induces the systemic hyperoxidation of peroxiredoxin in the mouse. (2015)
  • Author(s): Takujiro Homma, Satoshi Okano, Jaeyong Lee, Junitsu Ito, Noriyuki Otsuki, Toshihiro Kurahashi, Eun Sil Kang, Osamu Nakajima, and Junichi Fujii
  • Journal Title: Biochem Biophys Res Commun Volume: 463 Issue: 4 Pages: 1040-1046
  • DOI: 10.1016/j.bbrc.2015.06.055
  • Peer Reviewed
• [Journal Article] Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals (2014)
  • Author(s): Toshihiro Kurahashi a, Myoungsu Kwona, Takujiro Hommaa, Yuka Saito a, Jaeyong Lee a, Motoko Takahashi b, Ken-ichi Yamadac, Satoshi Miyata d, Junichi Fujii
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 452 Issue: 1 Pages: 136-141
  • DOI: 10.1016/j.bbrc.2014.08.072
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Kidney fibrosis is independent of the amount of ascorbic acid in mice with unilateral ureteral obstruction (2014)
  • Author(s): Nishida H, Kurahashi T, Saito Y, Otsuki N, Kwon M, Ohtake H H, Yamakawa M, Yamada K, Miyata S, Tomita Y, Fujiia J
  • Journal Title: Free Radical Res Volume: 48 Issue: 9 Pages: 1115-1124
  • DOI: 10.3109/10715762.2014.915031
  • Peer Reviewed
• [Journal Article] Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a-knockoutmice (2014)
  • Author(s): Junitsu Ito a,Noriyuki Otsuki a, Xuhong Zhang a, Tasuku Konno a, Toshihiro Kurahashi a,Motoko Takahashi b, Mayumi YamaKen-ichi Yamada d, Satoshi Miyata e, Junichi Fujiito c,YutaMatsuoka d,
  • Journal Title: Life Sciences Volume: 95 Issue: 1 Pages: 1-8
  • DOI: 10.1016/j.lfs.2013.12.004
  • Peer Reviewed
• [Journal Article] Differential responses of SOD1-deficient mouse embryonic fibroblasts to oxygen concentrations. (2013)
  • Author(s): Tsunoda S, Kibe N, Kurahashi T, and Fujii J.
  • Journal Title: Arch. Biochem. Biophys. Volume: 537 Issue: 1 Pages: 5-11
  • DOI: 10.1016/j.abb.2013.06.008
  • Peer Reviewed
• [Presentation] 酸化ストレスによるオートファジー障害に起因する脂質代謝異常 (2015)
  • Author(s): 倉橋敏裕、李在勇、白土貴也、浜島真司、本間拓二郎、白澤信行、藤井 順逸
  • Organizer: 第38回 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド、神戸市
  • Year and Date: 2015-12-01
• [Presentation] アスコルビン酸によるアセトアミノフェン誘導性酸化ストレスからの肝臓保護作用 (2015)
  • Author(s): 倉橋敏裕、鍋島篤典、李在勇、本間拓二郎、山田壮亮、中山敏幸、宮田哲、藤井 順逸
  • Organizer: 第68回 日本酸化ストレス学会学術集会
  • Place of Presentation: かごしま県民交流センター、鹿児島市
  • Year and Date: 2015-06-11
• [Presentation] 薬剤性急性肝障害に対するアスコルビン酸の肝臓保護作用 (2015)
  • Author(s): 倉橋敏裕、鍋島篤典、齋藤由佳、李在勇、本間拓二郎、山田壮亮、中山敏幸、宮田哲、藤井 順逸
  • Organizer: 第81回 日本生化学会東北支部会
  • Place of Presentation: 東北大学、仙台市
  • Year and Date: 2015-05-19
• [Presentation] アセトアミノフェン急性肝障害におけるアスコルビン酸とチオール化合物の肝臓保護作用 (2014)
  • Author(s): 倉橋敏裕、鍋島篤典、齋藤由香、李在勇、本間拓二郎、山田壮亮、 中山敏幸、佐藤英世、宮田哲、藤井順逸
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 臓器線維化における細胞外基質蛋白質の酸化的折畳みに働く小胞体チオールオキシダーゼとアスコルビン酸に関する研究 (2014)
  • Author(s): 倉橋敏裕、西田隼人、齋藤由香、李在勇、鍋島篤典、山田壮亮、 冨田善彦、宮田哲、高尾敏文、藤井順逸
  • Organizer: 日本酸化ストレス学会
  • Place of Presentation: 同志社大学（京都）
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] 臓器の線維化における細胞外基質タンパク質の酸化的折畳み機構に関する研究 (2014)
  • Author(s): 倉橋敏裕、西田隼人、齋藤由香、李在勇、鍋島篤典、山田壮亮、 冨田善彦、宮田哲、高尾敏文、藤井順逸
  • Organizer: 生化学会東北支部会
  • Place of Presentation: アキタパークホテル（秋田）
  • Year and Date: 2014-05-10
• [Presentation] The potential roles of PRDX4 as a thiol oxidase in endoplasmic reticulum. (2014)
  • Author(s): Toshihiro Kurahashi, Atsunori Nabeshima, Nobuyuki Shirasawa, Sohsuke Yamada, Junitsu Ito, Toshifumi Takao, and Junichi Fujii.
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International
  • Place of Presentation: Kyoto International Conference Center, Kyoto, JAPAN
• [Presentation] SOD1欠損による酸化的ストレスはPrdx4欠損マウスに肝障害を惹起する (2013)
  • Author(s): 倉橋敏裕、李在勇、鍋島篤典、山田壮亮、白澤信行、伊藤純一、藤井 順逸
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド、神戸
• [Presentation] Pleiotropic roles of Peroxiredoxin 4 in Antioxidation, Signal Regulation and Oxidative Protein Folding. (2013)
  • Author(s): Toshihiro Kurahashi, Atsunori Nabeshima, Nobuyuki Shirasawa, Sohsuke Yamada, Junitsu Ito, Toshifumi Takao, and Junichi Fujii.
  • Organizer: 6th Joint Meeting of the SFRR Australasia and Japan
  • Place of Presentation: Mercure Sydney Hotel, Sydney, Autralia
  • Invited
• [Remarks] 山形大学大学院 医学系研究科 生命環境医科学専攻 生化学・分子生物学講座
  • URL: http://www.id.yamagata-u.ac.jp/BiochemII/b2.html
• [Remarks] 山形大学大学院 医学系研究科 生命環境医科学専攻 生化学・分子生物学講座
  • URL: http://www.id.yamagata-u.ac.jp/BiochemII/b2.html