Proteome analysis for neuronal protection by hydrogen sulfide

• Project/Area Number: 18H02890
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: University of the Ryukyus
• Principal Investigator: KAKINOHANA MANABU 琉球大学, 医学(系)研究科(研究院), 教授 (20274897)
• Co-Investigator(Kenkyū-buntansha): 神里 興太 琉球大学, 医学(系)研究科(研究院), 助教 (10554454) ; 野口 信弘 琉球大学, 病院, 助教 (80457671) ; 西 啓亨 琉球大学, 医学部附属病院, 助教 (00610809)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2019: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 硫化水素ガス / 脊髄虚血 / 遅発性対麻痺 / 低体温療法 / 誘導型一酸化窒素合成酵素 / 硫化水素 / 遅発性脊髄障害 / 運動神経保護 / プロテオーム解析 / 遅発性脊髄運動神経障害 / Peroxiredoxin6 / プロ手オーム解析 / 硫化水素吸入 / 吸入療法 / 低体温 / 遅発性神経障害

Outline of Final Research Achievements

We found that hydrogen sulfide gas inhalation therapy suppressed the onset of delayed paraplegia in a mouse model of ischemic spinal cord injury, which is one of the complications after surgery such as aortic aneurysm. Our study, however, showed that this effect disappeared when combined with hypothermia. We conducted a study using proteomic analysis with the aim of investigating the factors responsible for this phenomenon. Our results suggested that the combined use of hydrogen sulfide gas inhalation therapy and hypothermia suppressed the expression of several protein molecules, among which the suppression of induced nitric oxide synthase (iNOS) was the most important factor. Furthermore, the iNOS knockout mice showed no effect of hydrogen sulfide gas inhalation therapy.

Academic Significance and Societal Importance of the Research Achievements

硫化水素ガスの生理学的意義については多様な機序が関わっていると報告されているが、我々の研究結果である脊髄虚血後の遅発性対麻痺発症に対する抑制効果についての詳細な機序は明らかとなっていなかった。今回の研究では、通常は神経保護効果のある低体温療法との併用で硫化水素ガスの効果が消失するという特徴を利用し、プロテオーム解析によりiNOSが重要であることが明らかとなったことは、学術的意義が高いと考えられる。

Research Products

• [Journal Article] Breathing hydrogen sulfide prevents delayed paraplegia in mice. (2019)
  • Author(s): Kakinohana M, Marutani E, Tokuda K, Kida K, Kosugi S, Kasamatsu S, Magliocca A, Ikeda K, Kai S, Sakaguchi M, Hirai S, Xian M, Kaneki M, Ichinose F.
  • Journal Title: Free Radic Biol Med Volume: 131 Pages: 243-250
  • DOI: 10.1016/j.freeradbiomed.2018.12.003
  • Peer Reviewed / Open Access / Int'l Joint Research