Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this be...Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.展开更多
Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidatio...Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidation stress of myocardial cells. Methods: Primary cultured neonate rat myocardial cells were cultured with TSN (1×10-4 mol/L) for 24 hours, and then the medium was supplemented with 200 μmol/L hydrogen peroxide for 2 h to initiate myocardial cell oxidative stress injury. PHB in myocardial cells was knocked down by small interfering RNA (siRNA), and the expression level of PHB was determined by western blot analysis. Flow cytometry was used to detect the apoptosis rate, intracellular calcium ion concentration ([Ca2+]i) and mitochondrial membrane potential (MMP). Results: The PHB expression, [Ca2+]i and the apoptotic rate significantly increased, and the MMP significantly decreased in the oxidative stress group compared with the control. The PHB expression, apoptosis rate and [Ca2+]i decreased, and MMP increased significantly in the TSN group compared with the oxidative stress group. Compared with the siRNA negative control group, the PHB expression level in myocardial cells was down-regulated, and the apoptosis rate and [Ca2+]i increased, and MMP decreased significantly in the siRNA group. Conclusion: TSN can reduce PHB expression in oxidative stress-injured myocardial cells hence protecting the myocardial cells.展开更多
文摘Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30572435)
文摘Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidation stress of myocardial cells. Methods: Primary cultured neonate rat myocardial cells were cultured with TSN (1×10-4 mol/L) for 24 hours, and then the medium was supplemented with 200 μmol/L hydrogen peroxide for 2 h to initiate myocardial cell oxidative stress injury. PHB in myocardial cells was knocked down by small interfering RNA (siRNA), and the expression level of PHB was determined by western blot analysis. Flow cytometry was used to detect the apoptosis rate, intracellular calcium ion concentration ([Ca2+]i) and mitochondrial membrane potential (MMP). Results: The PHB expression, [Ca2+]i and the apoptotic rate significantly increased, and the MMP significantly decreased in the oxidative stress group compared with the control. The PHB expression, apoptosis rate and [Ca2+]i decreased, and MMP increased significantly in the TSN group compared with the oxidative stress group. Compared with the siRNA negative control group, the PHB expression level in myocardial cells was down-regulated, and the apoptosis rate and [Ca2+]i increased, and MMP decreased significantly in the siRNA group. Conclusion: TSN can reduce PHB expression in oxidative stress-injured myocardial cells hence protecting the myocardial cells.
