Identification of oxidative stress sensors in TRPM7 channel

2016 Fiscal Year Final Research Report

• Project/Area Number: 25460302
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Tokyo Medical University
• Principal Investigator: Inoue Hana 東京医科大学, 医学部, 講師 (20390700)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: TRPM7 / 酸化ストレス

Outline of Final Research Achievements

TRPM7 is a non-selective cation channel harboring an alpha-kinase domain in its carboxyl terminal, expressed ubiquitously in animal cells. Since TRPM7 gene-deficient mice are embryonic lethal, it has been considered that TRPM7 plays an important role in development. In the present study, we explored mechanisms for the regulation of TRPM7 channel activity by oxidative stress. Using patch-clamp technique, it was revealed that the current of TRPM7 was inhibited by oxidative stress induced by an application of hydrogen peroxide in a free [Mg2+]i- and total [ATP]i-dependent manner. The current of a kinase-deficient TRPM7 mutant was similarly inhibited by hydrogen peroxide, therefore the kinase activity of TRPM7 was not involved in the current inhibition. Moreover, site-directed mutagenesis revealed that cysteine residues (C1809 and C1813) located in the zinc finger motif at the carboxyl terminal of TRPM7 was the most plausible candidate that senses oxidative stress.

Free Research Field

生理学