The role of S-nitrosylation for pathological mechanisms of metabolic syndrome.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860231
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SHINOZAKI SHOHEI 東京医科歯科大学, 医歯(薬)学総合研究科, 寄附講座准教授 (40622626)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: S-ニトロソ化 / 慢性炎症 / 加齢関連疾患 / SIRT1 / メタボリックシンドローム / 一酸化窒素

Outline of Final Research Achievements

In aging-related diseases, chronic inflammation is associated with the increased production of nitric oxide. Nitric oxide causes a posttranslational modification of proteins known as S-nitrosylation. SIRT1 is a protein deacetylase that inhibits the transcription factors p53 and NF-κB, which are involved in mediating cell death by apoptosis and promoting inflammatory responses. S-nitrosylation inhibits SIRT1 activity. We found that in cultured mammalian cells, S-nitrosylation of SIRT1 prevented it from deacetylating and inhibiting p53 and NF-κB. In mouse models of systemic inflammation, neurodegeneration or muscle aging, S-nitrosylation of SIRT1 and the associated activation of p53 and NF-κB required the activity of nitric oxide synthases. Thus, S-nitrosylation of SIRT1 may be a critical factor in promoting apoptotic and inflammatory responses in aging-related diseases.

Free Research Field

糖尿病　動脈硬化