Regulatory mechanisms of redox signal transduction mediated by endogenous electrophiles

• Project/Area Number: 24390082
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kumamoto University (2012, 2014); Tohoku University (2013)
• Principal Investigator: SAWA Tomohiro 熊本大学, 生命科学研究部, 教授 (30284756)
• Co-Investigator(Kenkyū-buntansha): AKAIKE Takaaki 東北大学, 大学院医学系研究科, 教授 (20231798) ; YOSHITAKE Jun 国立長寿医療研究センター, 研究院 (70414349)
• Co-Investigator(Renkei-kenkyūsha): KUMAGAI Yoshito 筑波大学, 大学院人間総合科学研究科, 教授 (00250100)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
• Keywords: 活性酸素 / 酸化ストレス / シグナル伝達 / レドックス / 親電子

Outline of Final Research Achievements

This study identified the endogenous formation of cysteine persulfide species that brings additional sulfur atom to cysteine thiol. It is noteworthy that cysteine persulfide species are capable of metabolizing reactive oxygen species and their second messenger molecules such as 8-nitro-cGMP. Further study is warranted to clarify regulatory mechanisms of cycteine persulfide species formation as well as their biological functions.

Research Products

• [Journal Article] 細菌の硫化水素・RSSの代謝シグナル制御 (2015)
  • Author(s): 津々木博康、小野勝彦、澤 智裕
  • Journal Title: 細胞工学 Volume: 34 Pages: 392-395
• [Journal Article] Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. (2014)
  • Author(s): Ida T, Sawa T, Ihara H, Tsucr iya Y, Watanabe Y, Kumagai Y, Suematsu M, Motohashi H, Fujii S. Matsunaga T, Yamamoto M, Ono K, Devarie-Baez N O, Xian M, Fukuto J M, Akaike T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: (印刷中) Issue: 21 Pages: 7606-7611
  • DOI: 10.1073/pnas.1321232111
  • Peer Reviewed / Open Access
• [Journal Article] The redox chemistry and chemical biology of H2S, hydropersulfides and derivaed species: implications to their possible biological activity and utility. (2014)
  • Author(s): Ono, K., Akaike T., Sawa, T., Kumagai, Y., Wink, D. A., Tantillo, D. J., Hobbs, A. J., Nagy, P., Xian, M., Lin, J., Fukuto, J.
  • Journal Title: Free Radic. Biol. Med. Volume: 77 Pages: 82-94
  • DOI: 10.1016/j.freeradbiomed.2014.09.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 活性酸素と炎症 (2014)
  • Author(s): 井田智章、赤池孝章、澤 智裕、藤井重元．
  • Journal Title: 感染・炎症・免疫 Volume: 44 Pages: 16-21
• [Journal Article] S-Guanylation proteomics for redox-based mitochondrial signaling. (2014)
  • Author(s): Rahaman MM, Sawa T, Ahtesh am AK, Khan S, Inoue H, Irie A. Fujii S, and Akaike T.
  • Journal Title: Antioxid. Redox Signal. Volume: 20 Issue: 2 Pages: 295-307
  • DOI: 10.1089/ars.2012.4606
  • Peer Reviewed / Open Access
• [Journal Article] Redox signal regulation via nNOS phosphorylation at Ser847 in PC12 cells and rat cerebellar granule neurons. (2014)
  • Author(s): Kasamats S, Watanabe Y, Sawa T, Akaike T, Ihara H.
  • Journal Title: Biochem. J. Volume: 459 Issue: 2 Pages: 251-263
  • DOI: 10.1042/bj20131262
  • Peer Reviewed
• [Journal Article] SIRT7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway. (2014)
  • Author(s): Yoshizawa T, Karim Md. F, Sato Y, Senokuchi T, Miyata K, Fukuda T, Go C, Tasaki M, Uchimura K, Kadomatsu T, Tian Z, Smolka C, Sawa T, Kakeya M, Tomizawa K, Ando Y, Araki E, Akaike T, Braun T, Oike Y, Bober E, Yamagata K.
  • Journal Title: Cell Metab. Volume: 9 Issue: 4 Pages: 712-721
  • DOI: 10.1016/j.cmet.2014.03.006
  • Peer Reviewed / Open Access
• [Journal Article] Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide. (2013)
  • Author(s): Sawa T, Ihara H, Ida T, Fujii S, Nishida M and Akaike T.
  • Journal Title: Nitric Oxide Volume: 34 Pages: 10-18
  • DOI: 10.1016/j.niox.2013.04.004
  • Peer Reviewed
• [Journal Article] Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria. (2013)
  • Author(s): Ito C, Saito Y, Nozawa T, Fujii S, Sawa T, Inoue H, Matsunaga T, Khan S, Akashi S, Hashimoto R, Aikawa C, Takahashi E, Sagara H, Komatsu M, Tanaka K, Akaike T, Nakagawa I, Arimoto H.
  • Journal Title: Mol. Cell Volume: 52 Issue: 6 Pages: 794-804
  • DOI: 10.1016/j.molcel.2013.10.024
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of H3K18 deacetylation of SIRT7 by Myb-binding protein la (Mybbpla) (2013)
  • Author(s): Karim Md F, Yoshizawa T, Sato Y, Sawa T, Tomizawa K, A kaike T and Yamagata K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 441 Issue: 1 Pages: 157-163
  • DOI: 10.1016/j.bbrc.2013.10.020
  • Peer Reviewed
• [Journal Article] Fluorescent probes for live cell imaging of endogenous guanine nitration (2013)
  • Author(s): Saito Y, Ito C, Fujii S, Sawa T, Akaike T and Arimoto H.
  • Journal Title: Chembiochem. Volume: 14 Issue: 9 Pages: 1068-1071
  • DOI: 10.1002/cbic.201300129
  • Peer Reviewed
• [Journal Article] Nitrated cyclic GMP modulates guard cell signaling in Arabidopsis (2013)
  • Author(s): Joudoi T, Hatakeyama T, Maeda T, Akaike T, Sawa T and Iwai S.
  • Journal Title: Plant Cell Volume: 25 Issue: 2 Pages: 558-571
  • DOI: 10.1105/tpc.112.105049
  • Peer Reviewed
• [Journal Article] Nitric oxide/soluble guanylyl cyclase signaling mediates depolarization-induced protection of rat mesencephalic dopaminergic neurons from MPP+ cytotoxicity (2013)
  • Author(s): Kurauchi Y, Hisatsune A, Isohama Y, Sawa T, Akaike T and Katsuki H.
  • Journal Title: Neurosci. Volume: 231 Pages: 206-215
  • DOI: 10.1016/j.neuroscience.2012.11.044
  • Peer Reviewed
• [Journal Article] S-nitrosylated a-l-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis (2013)
  • Author(s): Watanabe K, Ishima Y, Akaike T, Sawa T, Kuroda T, Ogawa W, Watanabe H, Suenaga A, Kai T, Otagiri M, and Maruyama T.
  • Journal Title: FASEB J Volume: 27 Issue: 1 Pages: 391-398
  • DOI: 10.1096/fj.12-217794
  • Peer Reviewed
• [Journal Article] NOシグナリング研究の最前線 (2013)
  • Author(s): 澤 智裕、赤池孝章
  • Journal Title: Heart View Volume: 17 Pages: 88-92
• [Journal Article] 活性酸素とガス状分子のシグナルネットワーク (2013)
  • Author(s): 澤 智裕、赤池孝章
  • Journal Title: 医学のあゆみ Volume: 247 Pages: 776-780
• [Journal Article] Nitric oxide/soluble guanylyl cyclase signaling mediates depolarization-induced protection of rat mesencephalic dopaminergic neurons from MPP+ cytotoxicity (2013)
  • Author(s): Kurauchi, Y., Sawa, T., et al.
  • Journal Title: Neurosci. Volume: 231 Pages: 206-215
  • Peer Reviewed
• [Journal Article] S-nitrosylated α-1-acid glycoprotein kills drug-resistant bacteria and aids survival in Sepsis (2013)
  • Author(s): Watanabe, K., Sawa, T., et al.
  • Journal Title: FASEB J. Volume: 27 Pages: 391-398
  • Peer Reviewed
• [Journal Article] S-Guanylation proteomics for redox-based mitochondrial signaling (2013)
  • Author(s): Rahaman, Md. M., Sawa, T., et al.
  • Journal Title: Antioxid.Redox Signal. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] 心不全におけるGタンパク質の酸化修飾と活性酸素・親電子シグナル制御 (2013)
  • Author(s): 西田基宏、澤智裕
  • Journal Title: 細胞工学 Volume: 31 Pages: 150-154
• [Journal Article] NOシグナリング研究の最前線 (2013)
  • Author(s): 澤智裕、赤池孝章
  • Journal Title: Heart View Volume: (印刷中)
• [Journal Article] Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration (2012)
  • Author(s): Nishida, M, Sawa, T., et al.
  • Journal Title: Nature Chem.Biol. Volume: 8 Pages: 714-724
  • Peer Reviewed
• [Journal Article] S-guanylation of human serum albumin is a unique posttranslational modification and results in a novel class of antibacterial agents (2012)
  • Author(s): Ishima, Y., Sawa, T., et al.
  • Journal Title: J. Pharm. Sci. Volume: 101 Pages: 3222-3229
  • Peer Reviewed
• [Journal Article] Anks4b, a novel target of HNF4α protein, interacts with GRP78 protein and regulates endoplasmic reticulum stress-induced apoptosis in pancreatic β-cells (2012)
  • Author(s): Saito, Y., Sawa, T, et al.
  • Journal Title: J.Biol.Chem. Volume: 287 Pages: 23236-23245
  • Peer Reviewed
• [Journal Article] Nitric oxide promotes recycling of 8-nitro-cGMP, a cytoprotective mediator, into intact cGMP in cells (2012)
  • Author(s): Saito, Y., Sawa, T., et al.
  • Journal Title: Mol. BioSystems Volume: 8 Pages: 2909-2915
  • Peer Reviewed
• [Journal Article] Nitrated cGMP : a new player in guard cell signaling (2012)
  • Author(s): Joudoi, T., Sawa, T., et al.
  • Journal Title: Plant Cell Volume: 25 Pages: 558-571
  • Peer Reviewed
• [Journal Article] 活性酸素のシグナル伝達系と分子標的 (2012)
  • Author(s): 澤智裕、赤池孝章
  • Journal Title: 日本臨床(増刊号) Volume: 70 Pages: 273-276
• [Journal Article] ROS・親電子リガンドとガス状分子のシグナルネットワーク (2012)
  • Author(s): 澤智裕、赤池孝章
  • Journal Title: 実験医学(増刊) Volume: 30 Pages: 64-69
• [Presentation] Persistent activation of protein kinase G via protein S-guanylation: Implication for endotoxin shock. (2015)
  • Author(s): 澤 智裕、小野勝彦、Ahtesham Ahmed、津々木博康、井田智章、藤井重元、赤池孝章．
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 長良川国際会議場（岐阜）
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 過イオウ化システインメタボローム解析による新規レドックス制御機構の解明 (2013)
  • Author(s): 澤智裕、井田智章、居原秀、赤池孝章
  • Organizer: 第62回日本酸化ストレス学会学術集会
  • Place of Presentation: 愛知県名古屋市
• [Presentation] ポリサルファーバイオロジーによるROS・NOシグナル制御 (2013)
  • Author(s): 澤智裕、井田智章、赤池孝章
  • Organizer: 第13回日本NO学会学術集会
  • Place of Presentation: 沖縄県那覇市
• [Presentation] 過イオウ化システイン誘導体による活性酸素シグナル制御 (2013)
  • Author(s): 澤智裕、井田智章、赤池孝章
  • Organizer: 第24回日本生体防御学会学術総会
  • Place of Presentation: 熊本県熊本市
• [Presentation] Mass spectrometric identification of unique polysulfides in biological systems (2012)
  • Author(s): Sawa, T., Ida, T. and Akaike, T
  • Organizer: International Symposium 2012 on Signaling Functions of Reactive Oxygen Species
  • Place of Presentation: 九州大学(福岡市)
  • Year and Date: 2012-12-17
• [Presentation] 活性酸素・NOによるヌクレオチドニトロ化修飾と塩基損傷応答 (2012)
  • Author(s): 澤智裕、赤池孝章
  • Organizer: 第84回日本遺伝学会
  • Place of Presentation: 九州大学(福岡市)
  • Year and Date: 2012-09-26
• [Presentation] NOの多様性にケミカルバイオロジーで迫る! (2012)
  • Author(s): 澤智裕、赤池孝章
  • Organizer: 第121回日本薬理学会近畿部会新薬理学セミナー
  • Place of Presentation: 徳島大学(徳島市)(招待講演)
  • Year and Date: 2012-06-30
• [Presentation] ROS signaling via 8-nitro-cGMP formation and protein S-guanylation (2012)
  • Author(s): Sawa, T., et al.
  • Organizer: The 33rd Naito Conference
  • Place of Presentation: ガトーキングダムサッポロ(札幌市)
• [Presentation] S-Guanylation proteomics for redox-based mitochondrial signaling (2012)
  • Author(s): Sawa, T., et al.
  • Organizer: The 7th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Edinburgh, UK
• [Presentation] ミトコンドリアスーパーオキシドならびにNADPHオキシダーゼに依存したニトロ化cGMPの生成 : NOおよびROSシグナルへの関与 (2012)
  • Author(s): 澤智裕、他
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Remarks] 熊本大学大学院生命科学研究部微生物学分野ホームページ
  • URL: http://kumadai-bisei.com/
• [Remarks] 東北大学大学院医学系研究科環境保健医学分野
  • URL: http://www.toxicosci.med.tohoku.ac.jp/
• [Remarks]
  • URL: http://kumadai-bisei.com/