Evaluation of sirtuin roles in septic shock

• Project/Area Number: 24590535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Juntendo University
• Principal Investigator: MURAKAMI Taisuke 順天堂大学, 医学部, 助教 (40384135)
• Co-Investigator(Kenkyū-buntansha): NAGAOKA Isao 順天堂大学, 医学部, 教授 (60164399) ; IBA Toshiaki 順天堂大学, 医学部, 教授 (40193635)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 敗血症 / サーチュイン / Lipopolysaccharide / 翻訳後修飾 / sirtuin / LPS (lipopolysaccharide) / lipopolysaccharide / Sirtuin（サーチュイン）

Outline of Final Research Achievements

SIRT1 epigenetically regulates multiple physiological systems such as senescence, metabolism, and inflammation by acetylating their regulatory factors. In this study, we evaluated the effect of SIRT1 regulation on sepsis.
SIRT1 selective activator was found to suppress the release of IL-6 from LPS-stimulated mouse macrophage-like RAW264.7 cells, while selective inhibitor not affected the release. Intraperitoneal injection of SIRT1 activator suppressed and increased serum inflammatory cytokines and survival rate, respectively in cecal ligation and puncture (CLP) induced septic mice. Unlike in vitro results, SIRT1 inhibitor also suppressed the inflammatory cytokine, and slightly increased the survival rate of CLP mice.
Taken together, our results suggest that modulation of SIRT1 can potently regulate the production of inflammatory cytokine, which is involved in the pathogenesis of septic shock.

Research Products

• [Journal Article] Release mechanism of high mobility group nucleosome binding protein 1 from lipopolysaccharide-stimulated macrophages. (2016)
  • Author(s): Murakami T, Hu Z, Tamura H, Nagaoka I
  • Journal Title: Mol Med Rep Volume: 13 Issue: 4 Pages: 3115-3120
  • DOI: 10.3892/mmr.2016.4893
  • Peer Reviewed
• [Presentation] Mechanism for the lipopolysaccharide-induced release of high mobility group nucleosome-binding domain-1 from murine macrophage like RAW264.7. (2015)
  • Author(s): Murakami T, Hu Z, Suzuki K, Tamura H, Nagaoka I
  • Organizer: 48Th Annual Meeting of the Society for Leukocyte Biology
  • Place of Presentation: Hilton North Raleigh Midtown hotel,Raleigh, NC, US
  • Year and Date: 2015-09-27
  • Int'l Joint Research