Rho-kinase signaling pathway promotes the expression of PARP to accelerate cardiomyocyte apoptosis in ischemia/reperfusion

Abstract

It has been previously reported that Rho-kinase (ROCK) and poly ADP-ribose polymerase (PARP) serve critical roles in myocardial ischemia/reperfusion (I/R) injury. Studies have additionally demonstrated that the activation of ROCK and the expression of PARP are increased in I/R. However, the effect and mechanism of the two proteins remains to be fully elucidated in I/R. In addition, whether they can be influenced by each other is unclear. In the present study, it was demonstrated that ischemia followed by reperfusion resulted in a significant increase in ROCK and PARP. In addition, Y-27632 (ROCK inhibitor) and 3-aminobenzamide (3-AB; PARP inhibitor) pretreatment rescued myocardial infarction size and cardiomyocyte apoptosis. The inhibitory role of Y-27632 was observed to be superior to that of the 3-AB group. In addition, Y-27632 and 3-AB diminished extracellular signal-related kinase (ERK) phosphorylation and the production of tumor necrosis factor α and interleukin 6. Overall, the results of the present study suggested that the inhibition of ROCK leads to reduced myocardial infarction size and cardiomyocyte apoptosis via the PARP/ERK signaling pathway.

Remote ischemic post‑conditioning protects against myocardial ischemia/reperfusion injury by inhibiting the Rho‑kinase signaling pathway

“…Both ROCK1 and ROCK2 are expressed in vascular smooth muscle and the heart (17,18). An increasing body of evidence has demonstrated that the Rho-kinase pathway serves an important role in myocardial I/R damage and inhibition of the Rho-kinase signaling pathway has beneficial effects on cardiac functions and apoptosis (20,34). Apoptosis is an essential contributor to cardiac dysfunction (35).…”

The E3 ubiquitin ligase MuRF2 attenuates LPS‐induced macrophage activation by inhibiting production of inflammatory cytokines and migration

“…The cultured cells were washed with cold PBS and lysed with RIPA lysis buffer (Beyotime Biotechnology, Shanghai, China) supplemented with a protease inhibitor ‘cocktail’. After the protein concentrations were measured using the bicinchoninic acid assay (Thermo Fisher Scientific), equal amounts of protein lysates were separated by SDS/PAGE and transferred to poly(vinylidene difluoride) membranes (Millipore, Billerica, MA, USA) for immunoblot analysis as described previously . The membranes were then incubated with the primary antibodies overnight at 4 °C.…”

The RhoA/ROCK pathway mediates high glucose‐induced cardiomyocyte apoptosis via oxidative stress, JNK, and p38MAPK pathways

“…Many studies have indicated that a key pathological consequence of sustained hyperglycemia is the induction of cardiomyocyte apoptosis in diabetic patients and animal models . Recent studies demonstrate that the RhoA/ROCK pathway regulates the activities of MAPKs . The purpose of the present study was to understand the roles of RhoA/ROCK in high glucose (HG)‐induced apoptosis and oxidative stress in cardiomyocytes in vitro and to identify the signalling cross talk between the RhoA/ROCK and MAPK pathways.…”