Targeting TRPM2 in ROS-Coupled Diseases.
Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a Ca(2+)-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca(2+) signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca(2+) through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca(2+) signaling in ROS-coupled diseases.
Division of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo 164-8530, Japan. s.yamamoto@thu.ac.jp.
Shinichiro
S
Yamamoto
Division of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo 164-8530, Japan. s.shimizu@thu.ac.jp.
Shunichi
S
Shimizu
Ca2+ signaling; ROS-coupled diseases; TRPM2; reactive oxygen species