Elucidation of mechanisms underlying regulation of inflammatory cellular responses by redox-sensitive TRP channels.

2015 Fiscal Year Final Research Report

• Project/Area Number: 24249017
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Mori Yasuo 京都大学, 地球環境学堂, 教授 (80212265)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: カルシウム / TRP / チャネル / レドックス / 活性酸素種 / 炎症

Outline of Final Research Achievements

Reactive oxygen species (ROS) and electrophiles, known to exert stress on organisms, are emerging as mediators of cellular signals. Transient Receptor Potential (TRP) Ca2+-permeable cation channels are activated by various triggers from outside and inside the cell. We and others have revealed that multiple redox-sensitive TRPs sense ROS to induce diverse physiological/pathological responses, such as cell death, chemotaxis, and pain transduction. TRPs sense ROS/electrophiles either indirectly through second messengers or directly via oxidative modification of cysteine residues. In this project, I clarified roles of redox-sensitive TRPs in inflammation. In particular, TRPM2 turned out to be a key signal regulator for diverse inflammatory cellular responses. Also, TRPA1 showed a unique, high sensitivity to oxidants including O2. Understanding the physiological significance of redox-sensitive TRPs will lead us to consider these TRP channels as viable therapeutic targets.

Free Research Field

生化学