Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarge...Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.展开更多
Aim Endoplasmic reticulum （ER） stress is increasingly recognized as an important contributor to the pathophysiology of many diseases, and therapeutic interventions that target ER stress response emerge as new thera-...Aim Endoplasmic reticulum （ER） stress is increasingly recognized as an important contributor to the pathophysiology of many diseases, and therapeutic interventions that target ER stress response emerge as new thera- peutic modalities to treat cardiovascular diseases driven by prolonged ER stress. Ginkgolides K （GK） is a diterpene lactone constituent isolated from the leaves of Ginkgo biloba and has been found to possess potent neuroprotective properties. This study is aimed to investigate the cytoprotective effect of GK in cultured cardiomyocytes subjected to ER stress injury. Neonatal rat cardiomyocytes （NRCMs） were treated with ER stress inducer tunicamycin to mimic the ER stress injury. We demonstrated that GK pre-treatment mitigated ER stress-induced apoptosis in tunicamycin treated NRCMs. We observed that the activation of ER-associated degradation （ERAD） and autophagy were in- volved in the ER stress inhibition exerted by GK. These beneficial effects of GK were nearly abolished by the addi- tion of specific short interfering RNA （siRNA） for IRElα and XBP-1. Therefore, we conclude that GK might be a promising therapeutic agent for ER stress-mediated cardiovascular diseases, and ER-associated degradation （ERAD） and autophagy play a vital role in GK mediated cytoprotection.展开更多
AIM:To observe the protective effects of 13-methyltetradecanoic acid(13-MTD)on the injury of cultured brain microvascular endothelial cells(BMECs)induced by oxygen paradox. METHODS:Two screen filtration methods and en...AIM:To observe the protective effects of 13-methyltetradecanoic acid(13-MTD)on the injury of cultured brain microvascular endothelial cells(BMECs)induced by oxygen paradox. METHODS:Two screen filtration methods and enzyme digestion method were used to the primary culture and subculture of the neonatal rat cortex BMECs.展开更多
Background Neonatal mouse heart can completely regenerate after amputating 15%of ventricular apex.However,the regenerative ability is lost by 7 day-post-birth.Cardiomyocyte dedifferentiation is the only way of existin...Background Neonatal mouse heart can completely regenerate after amputating 15%of ventricular apex.However,the regenerative ability is lost by 7 day-post-birth.Cardiomyocyte dedifferentiation is the only way of existing myocytes returning to cell cycle and initiating proliferation.Oncostatin M(OSM)was demonstrated to promote cardiomyocyte dedifferentiation after cardiac injury,while its role in heart regeneration has not been addressed.Modulating the progress of dedifferentiationproliferation through OSM may provide a clinical therapy for preventing further deterioration of patients with heart injury and restoring the lost myocardium.展开更多
文摘Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.
文摘Aim Endoplasmic reticulum （ER） stress is increasingly recognized as an important contributor to the pathophysiology of many diseases, and therapeutic interventions that target ER stress response emerge as new thera- peutic modalities to treat cardiovascular diseases driven by prolonged ER stress. Ginkgolides K （GK） is a diterpene lactone constituent isolated from the leaves of Ginkgo biloba and has been found to possess potent neuroprotective properties. This study is aimed to investigate the cytoprotective effect of GK in cultured cardiomyocytes subjected to ER stress injury. Neonatal rat cardiomyocytes （NRCMs） were treated with ER stress inducer tunicamycin to mimic the ER stress injury. We demonstrated that GK pre-treatment mitigated ER stress-induced apoptosis in tunicamycin treated NRCMs. We observed that the activation of ER-associated degradation （ERAD） and autophagy were in- volved in the ER stress inhibition exerted by GK. These beneficial effects of GK were nearly abolished by the addi- tion of specific short interfering RNA （siRNA） for IRElα and XBP-1. Therefore, we conclude that GK might be a promising therapeutic agent for ER stress-mediated cardiovascular diseases, and ER-associated degradation （ERAD） and autophagy play a vital role in GK mediated cytoprotection.
基金Supported by the Science & Technology Project of Fujian Province(2010Y0027)
文摘AIM:To observe the protective effects of 13-methyltetradecanoic acid(13-MTD)on the injury of cultured brain microvascular endothelial cells(BMECs)induced by oxygen paradox. METHODS:Two screen filtration methods and enzyme digestion method were used to the primary culture and subculture of the neonatal rat cortex BMECs.
文摘Background Neonatal mouse heart can completely regenerate after amputating 15%of ventricular apex.However,the regenerative ability is lost by 7 day-post-birth.Cardiomyocyte dedifferentiation is the only way of existing myocytes returning to cell cycle and initiating proliferation.Oncostatin M(OSM)was demonstrated to promote cardiomyocyte dedifferentiation after cardiac injury,while its role in heart regeneration has not been addressed.Modulating the progress of dedifferentiationproliferation through OSM may provide a clinical therapy for preventing further deterioration of patients with heart injury and restoring the lost myocardium.
