SIRT1 expression, activity and NAD+ regulation using noncancerous liver tissue specimens from hepatocellular carcinoma patients with non-B non-C hepatitis.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861197
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: KONISHI Hideyuki 九州大学, 医学(系)研究科(研究院), 研究員 (80634211)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: NASH / SIRT1 / 肝炎 / NAD代謝

Outline of Final Research Achievements

We demonstrate SIRT1 expression, activity and NAD+ regulation using noncancerous liver tissue specimens from hepatocellular carcinoma patients with non-B non-C (NBNC) hepatitis. SIRT1 expression levels were higher in NBNC patients than in healthy donors, while SIRT1 histone H3K9 deacetylation activity was suppressed. In the liver of hepatitis patients, decreased NAD+ amounts and its regulatory enzyme NAMPT expression levels were observed, and this led to inhibition of SIRT1. SIRT1 expression was associated with HIF1 protein accumulation in both the NBNC liver and liver cancer cell lines. In HepG2 cells, hypoxia induced inflammatory chemokines. These inductions were suppressed in rich NAD+ condition, and by SIRT1 activator treatment. In conclusion, hepatic SIRT1 activity was repressed in NBNC patients, and normalization of NAD+ amounts and activation of SIRT1 could improve the inflammatory condition in the liver of NBNC hepatitis patients.

Free Research Field

肝炎、免疫