RhoA is a small GTPase protein.Its downstream effector protein Rho kinase(ROCK)regulates a variety of cell functions,including cell growth,gene expression and cytoskeleton recombination.Studies have demonstrated that ...RhoA is a small GTPase protein.Its downstream effector protein Rho kinase(ROCK)regulates a variety of cell functions,including cell growth,gene expression and cytoskeleton recombination.Studies have demonstrated that this pathway plays an important pathophysiological role in diabetic nephropathy and other complications,hypertension,stroke,tumor,osteoarthritis,acute lung injury and other diseases.The occurrence and development of diabetes-related disease is closely related to the activation or up-regulation of RhoA/ROCK pathway.As a key target of drug development,ROCK inhibitors have been widely concerned by scholars.This article reviews the relationship between RhoA/ROCK pathway and diabetesrelated disease,and offers a new and effective strategy for the prevention and treatment of this series of diseases.展开更多
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 ...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 rales after 1 h,3 h,6 h,9 h and 12 h of anoxia were recorded and the expressions of RhoA,ROCK1/2,p-PI3 K,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.9h and 12 h decreased gradually but the apoptosis rates increased gradually,and the expressions of RhoA,ROCK1/2,p-P13 K,p-AKT and caspase-3 were increasing along with the increasing duration of anoxia.The apoptotic rales after 1 h,3 h,6 h.9 h and 12 h of anoxia were(4.36±0.98)%,(8.36±2.12)%,(15.32±3.62)%,(18.68±4.83)%and(24.56±6.22)%.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-PI3 K,p-AKT and caspase-3 decreased significantly(P<0.05).The apoptosis rate and the expressions of RhoA,ROCK1/2,p-PI3 K,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.展开更多
Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke,...Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.展开更多
基金National Natural Science Foundation of China(No.81660148)Innovation and Entrepreneurship Project of Science and Technology Bureau of Chengguan District of Lanzhou City(No.2018HFZ0068)Hospital cultivation Program of Gansu Provincial people's Hospital(No.19SYPYB-4).
文摘RhoA is a small GTPase protein.Its downstream effector protein Rho kinase(ROCK)regulates a variety of cell functions,including cell growth,gene expression and cytoskeleton recombination.Studies have demonstrated that this pathway plays an important pathophysiological role in diabetic nephropathy and other complications,hypertension,stroke,tumor,osteoarthritis,acute lung injury and other diseases.The occurrence and development of diabetes-related disease is closely related to the activation or up-regulation of RhoA/ROCK pathway.As a key target of drug development,ROCK inhibitors have been widely concerned by scholars.This article reviews the relationship between RhoA/ROCK pathway and diabetesrelated disease,and offers a new and effective strategy for the prevention and treatment of this series of diseases.
基金supported by the Science Foundation of Wuhan University(Grant No:201255M152)
文摘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 rales after 1 h,3 h,6 h,9 h and 12 h of anoxia were recorded and the expressions of RhoA,ROCK1/2,p-PI3 K,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.9h and 12 h decreased gradually but the apoptosis rates increased gradually,and the expressions of RhoA,ROCK1/2,p-P13 K,p-AKT and caspase-3 were increasing along with the increasing duration of anoxia.The apoptotic rales after 1 h,3 h,6 h.9 h and 12 h of anoxia were(4.36±0.98)%,(8.36±2.12)%,(15.32±3.62)%,(18.68±4.83)%and(24.56±6.22)%.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-PI3 K,p-AKT and caspase-3 decreased significantly(P<0.05).The apoptosis rate and the expressions of RhoA,ROCK1/2,p-PI3 K,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.
基金supported by the National Natural Science Foundation of China(numbers:81774416 and 81473764)。
文摘Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.
