Fig 8.

Cartoon illustrating the CaM, GRK5 and class IIa HDACs translocation at pathological condition. Under stress (Ang II, PE or TAC), which increases the ROS level in the myocytes, CaM dissociates from RyR2 and translocation to the nucleus with GRK5 and causes nuclear export of class IIa HDACs. Treatment with suramin, which completely knock off the CaM from RyR2, promotes nuclear CaM accumulation together with GRK5 and there was enhanced nuclear export of class IIa HDACs. Conversely, dantrolene, RyR stabilizer, and amlexanox, GRK5 inhibitor, prevent the both CaM and GRK5 nuclear accumulation and suppressed the class IIa HDACs nuclear export. Our findings suggesting that dissociation of CaM from RyR2 drives CaM to the nucleus, together with GRK5 with parallel class IIa HDACs nuclear export, as a potentially important step driving pathological cardiac hypertrophy. DAN: dantrolene.