| First Author | Kitajima N | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 409 |
| Issue | 1 | Pages | 108-13 |
| PubMed ID | 21565173 | Mgi Jnum | J:172441 |
| Mgi Id | MGI:5007844 | Doi | 10.1016/j.bbrc.2011.04.124 |
| Citation | Kitajima N, et al. (2011) TRPC3-mediated Ca(2+) influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts. Biochem Biophys Res Commun 409(1):108-13 |
| abstractText | Dilated cardiomyopathy (DCM) is a myocardial disorder that is characterized by dilation and dysfunction of the left ventricle (LV). Accumulating evidence has implicated aberrant Ca(2+) signaling and oxidative stress in the progression of DCM, but the molecular details are unknown. In the present study, we report that inhibition of the transient receptor potential canonical 3 (TRPC3) channels partially prevents LV dilation and dysfunction in muscle LIM protein-deficient (MLP (-/-)) mice, a murine model of DCM. The expression level of TRPC3 and the activity of Ca(2+)/calmodulin-dependent kinase II (CaMKII) were increased in MLP (-/-) mouse hearts. Acitivity of Rac1, a small GTP-binding protein that participates in NADPH oxidase (Nox) activation, and the production of reactive oxygen species (ROS) were also increased in MLP (-/-) mouse hearts. Treatment with pyrazole-3, a TRPC3 selective inhibitor, strongly suppressed the increased activities of CaMKII and Rac1, as well as ROS production. In contrast, activation of TRPC3 by 1-oleoyl-2-acetyl-sn-glycerol (OAG), or by mechanical stretch, induced ROS production in rat neonatal cardiomyocytes. These results suggest that up-regulation of TRPC3 is responsible for the increase in CaMKII activity and the Nox-mediated ROS production in MLP (-/-) mouse cardiomyocytes, and that inhibition of TRPC3 is an effective therapeutic strategy to prevent the progression of DCM. |
