RhoA/ROCK pathway regulates hypoxia-induced myocardial cell apoptosis

Asian Pac J Trop Med. 2014 Nov;7(11):884-8. doi: 10.1016/S1995-7645(14)60154-1. Epub 2014 Oct 22.

Abstract

Objective: To observe the regulatory effects of RhoA/ROCK pathway on the apoptosis of cardiac myocyte induced by anoxia and its mechanism.

Methods: The model of cardiac myocyte anoxia was established. The beat pulsations and apoptosis rates after 1 h, 3 h, 6 h, 9 h and 12 h of anoxia were recorded and the expressions of RhoA, ROCK1/2, p-PI3K, p-AKT and caspae-3 were detected, too. The apoptosis and the expressions of related proteins were detected after RNAi of RhoA and the inhibition of ROCK by Y-27632.

Results: The beat pulsations after 1 h, 3 h, 6 h, 9 h and 12 h decreased gradually but the apoptosis rates increased gradually, and the expressions of RhoA, ROCK1/2, p-PI3K, p-AKT and caspase-3 were increasing along with the increasing duration of anoxia. The apoptotic rates after 1 h, 3 h, 6 h, 9 h and 12 h of anoxia were (4.360.98)%, (8.362.12)%, (15.323.62)%, (18.684.83)% and (24.566.22)%, respectively and decreased more significantly than control group in different time points of anoxia (P<0.05), and the expressions of RhoA, ROCK1/2, p-PI3K, p-AKT and caspase-3 decreased significantly (P<0.05). The apoptosis rate and the expressions of RhoA, ROCK1/2, p-PI3K, p-AKT and caspase-3 decreased significantly (P<0.05) after the inhibition of ROCK by Y-27632 (P<0.05).

Conclusions: RhoA/ROCK pathway plays a critical role in the regulation of the apoptosis of cardiac myocyte induced by anoxia, which may be accompanied by regulating the activity of PI3K/AKT/Caspase-3 pathway.

Keywords: Anoxia; Apoptosis; Cardiac myocyte; RNA interference; ROCK; RhoA.