Background AngiotensinⅡ(AngⅡ) plays a critical role in the pathophysiology of cardiovascular diseases. Recently,studies have shown that Endoplasmic Reticulum (ER) stress was activated in failure hearts.This study wa...Background AngiotensinⅡ(AngⅡ) plays a critical role in the pathophysiology of cardiovascular diseases. Recently,studies have shown that Endoplasmic Reticulum (ER) stress was activated in failure hearts.This study was designed to examine whether ER stress participates in the pathologic process of AngⅡ-induced cardiomyocytes apoptosis. Methods Neonatal rat cardiomyocytes were incubated with concentrations of AngⅡ(0,1,10,100 nmol/L) for 24 hours.Confocal fluorescence microscopy with double staining of TUNEL and CHOP detected the percentage of apoptotic cells.Levels of GRP78,JNK,p-JNK,CHOP and caspase-12 were analyzed by western blot.Telmisartan(10- ~6mol/L) was used to test the effects of ATI receptor on AngⅡ- induced cell apoptosis,ER stress chaperones and signaling molecules.Results Treatment with AngⅡat 1,10, and 100 nmol/L for 24 hours stimulated GRP78,JNK,p-JNK and CHOP protein production,and increased apoptosis of myocytes.The protein expression and the number of apoptotic cells were depedent on AngⅡconcentration.About 60%of apoptotic cells were CHOP positive at 10 and 100nmol/L AngⅡtreatment,while no CHOP positive apoptotic cells were found at myocytes under physiological condition and 1 nmo/L AngⅡtreatment.Telmisartan decreased signaling molecules expression and abolished ER stress-mediated apoptosis induced by 100 nmol/L AngⅡ.Conclusions These results indicate that ER stress may be involved in the mechanisms of AngⅡ-induced cardiomyocytes apoptosis.JNK, caspase12 and CHOP all participate in the pathologic process.展开更多
Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced...Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced carcinogenesis, the 'Oxidative Stress' theory has been postulated. In this review, in order to reconsider the significance of 'Oxidative Stress' to POP-induced carcinogenesis, we focus on in vivo studies examining formation of 8-hydroxydeoxyguanosine (8-OH -dG), a marker of oxidative DNA damage with mutagenic potential, after treatment of rodents with POPs. Some studies clearly demonstrated that 8-OH-dG levels in the liver DNA were increased by POP-treatments. These findings suggest that 'Oxidative Stress' could contribute as one factor to POP-induced carcinogenesis. Furthermore, we refer to other multiple biological changes caused by POP-treatment presumably contributing to the carcinogenic mechanisms, and consider possible roles of 'Oxidative Stress' in the carcinogenesis process展开更多
In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed：＇a granular background and details of a darker lacelike reticulum which in places appears to be made up...In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed：＇a granular background and details of a darker lacelike reticulum which in places appears to be made up of chains of＂vesicles＂＇（Porter et al.,1945）.This constituted the first published observation of the endoplasmic reticulum（ER）and,while it was not evident at that time,this cytoplasmic system of interconnecting membrane-lined channels, comprising vesicles, tubules and cisternae, has numerous important functions.展开更多
Experimental results of the temperature dependence of critical resolved. shear stresses (CRSS)of Mo, Fe, Al and Mg single crystals are shown. Associating reports in recent years, we point out that the approximate expo...Experimental results of the temperature dependence of critical resolved. shear stresses (CRSS)of Mo, Fe, Al and Mg single crystals are shown. Associating reports in recent years, we point out that the approximate exponential relationship between CRSS and the absolute temperatureat least in the region of the steep temperature dependence range of many materials is more common, even for bcc, fcc, and hcp single crystals. polycrystals and other covalent crystals,provided that the slip plane and slip direction are kept the same. Successful explanation with atomic force law shows that the interatomic forces (electronic structure) play a decisive role in determining the temperature dependence of yield stresses for a large number of materials.展开更多
文摘Background AngiotensinⅡ(AngⅡ) plays a critical role in the pathophysiology of cardiovascular diseases. Recently,studies have shown that Endoplasmic Reticulum (ER) stress was activated in failure hearts.This study was designed to examine whether ER stress participates in the pathologic process of AngⅡ-induced cardiomyocytes apoptosis. Methods Neonatal rat cardiomyocytes were incubated with concentrations of AngⅡ(0,1,10,100 nmol/L) for 24 hours.Confocal fluorescence microscopy with double staining of TUNEL and CHOP detected the percentage of apoptotic cells.Levels of GRP78,JNK,p-JNK,CHOP and caspase-12 were analyzed by western blot.Telmisartan(10- ~6mol/L) was used to test the effects of ATI receptor on AngⅡ- induced cell apoptosis,ER stress chaperones and signaling molecules.Results Treatment with AngⅡat 1,10, and 100 nmol/L for 24 hours stimulated GRP78,JNK,p-JNK and CHOP protein production,and increased apoptosis of myocytes.The protein expression and the number of apoptotic cells were depedent on AngⅡconcentration.About 60%of apoptotic cells were CHOP positive at 10 and 100nmol/L AngⅡtreatment,while no CHOP positive apoptotic cells were found at myocytes under physiological condition and 1 nmo/L AngⅡtreatment.Telmisartan decreased signaling molecules expression and abolished ER stress-mediated apoptosis induced by 100 nmol/L AngⅡ.Conclusions These results indicate that ER stress may be involved in the mechanisms of AngⅡ-induced cardiomyocytes apoptosis.JNK, caspase12 and CHOP all participate in the pathologic process.
文摘Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced carcinogenesis, the 'Oxidative Stress' theory has been postulated. In this review, in order to reconsider the significance of 'Oxidative Stress' to POP-induced carcinogenesis, we focus on in vivo studies examining formation of 8-hydroxydeoxyguanosine (8-OH -dG), a marker of oxidative DNA damage with mutagenic potential, after treatment of rodents with POPs. Some studies clearly demonstrated that 8-OH-dG levels in the liver DNA were increased by POP-treatments. These findings suggest that 'Oxidative Stress' could contribute as one factor to POP-induced carcinogenesis. Furthermore, we refer to other multiple biological changes caused by POP-treatment presumably contributing to the carcinogenic mechanisms, and consider possible roles of 'Oxidative Stress' in the carcinogenesis process
文摘In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed：＇a granular background and details of a darker lacelike reticulum which in places appears to be made up of chains of＂vesicles＂＇（Porter et al.,1945）.This constituted the first published observation of the endoplasmic reticulum（ER）and,while it was not evident at that time,this cytoplasmic system of interconnecting membrane-lined channels, comprising vesicles, tubules and cisternae, has numerous important functions.
文摘Experimental results of the temperature dependence of critical resolved. shear stresses (CRSS)of Mo, Fe, Al and Mg single crystals are shown. Associating reports in recent years, we point out that the approximate exponential relationship between CRSS and the absolute temperatureat least in the region of the steep temperature dependence range of many materials is more common, even for bcc, fcc, and hcp single crystals. polycrystals and other covalent crystals,provided that the slip plane and slip direction are kept the same. Successful explanation with atomic force law shows that the interatomic forces (electronic structure) play a decisive role in determining the temperature dependence of yield stresses for a large number of materials.
