Kazuhiro Nishiyama, Tomohiro Tanaka, Akiyuki Nishimura and Motohiro Nishida* Pages 1 - 9 ( 9 )
Background: Transient receptor potential (TRP) channels, especially canonical TRP channel subfamily members 3 (TRPC3) and 6 (TRPC6), have attracted attention as a putative therapeutic target of heart | 1 failure. Moreover, TRPC3 and TRPC6 channels are physiologically important for maintaining cellular homeostasis. How TRPC3/C6 channels alter intracellular signaling from adaptation to maladaptation has been discussed for many years. We recently showed that formation of a protein signal complex between TRPC3 and NADPH oxidase (Nox) 2 caused by environmental stresses (e.g., hypoxia, nutritional deficiency, and anticancer drug treatment) promotes Nox2-dependent reactive oxygen species production and cardiac stiffness, including myocardial atrophy and interstitial fibrosis, in rodents. In fact, pharmacological prevention of the TRPC3-Nox2 protein complex can maintain cardiac flexibility in mice after anti-cancer drug treatment.
Conclusion: In this mini-review, we discuss the relationship between TRPC3/C6 channels and cardiovascular disease, and propose a new therapeutic strategy by focusing on pathology-specific protein– protein interactions.
TRPC3, TRPC6, Nox2, oncocardiology, protein–protein interaction, drug repurposing
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences (NINS), Okazaki 444-8787, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582