AIM:To study the effect of breviscapine (Bre) on activity of protein kinase Cα (PKCα) and nuclear factor (NF)-κB in pancreas,and the mechanism of Bre attenuating acute pancreatitis (AP). METHODS:One hundred and eig...AIM:To study the effect of breviscapine (Bre) on activity of protein kinase Cα (PKCα) and nuclear factor (NF)-κB in pancreas,and the mechanism of Bre attenuating acute pancreatitis (AP). METHODS:One hundred and eight rats were randomly divided into acute necrotizing pancreatitis (ANP) group,Bre group (ANP + Bre group) and sham operation (SO) group,36 rats in each group. ANP model was induced by a retrograde injection of 4% sodium deoxycholate into the bilio-pancreatic duct. Fifteen minutes after the ANP model was induced,the rats in Bre group were intraperitoneally injected with Bre (0.4 mg/100 g body weight or 0.1 mL/100 g body weight). Survival time and mortality of rats were calculated. Serum amylase and malondialdehyde levels were measured,volume of ascites was recorded and morphology of pancreas and lung was evaluated at 1,5 and 10 h,after the ANP model was induced,respectively. Expressions of PKCα and subunit p65 of NF-κB in pancreas were detected by immunohistochemistry and Western blotting. RESULTS:The life span of rats was longer and the mortality was lower in Bre group than in ANP group 13.51 ± 5.46 vs 25.36 ± 8.11 (P < 0.05). The amylase and MDA levels as well as the volume of ascites were lower and the pathological changes in pancreas and lung were less in Bre group than ANP group (P < 0.05),indicating that the pancreatitis is less severe in Bre group than ANP group. The activation of PKCα and NF-κB p65 in pancreas was induced rapidly and reached their peak at 1 h or 5 h after ANP,but their activity in Bre group was significantly inhibited. CONCLUSION:Bre exerts its therapeutic effect on AP by inhibiting the activation of PKCα and NF-κB p65 in pancreas.展开更多
Elucidating protein translational regulation is crucial for understanding cellular function and drug development.A key molecule in protein translation is ribosome,which is a super-molecular complex extensively studied...Elucidating protein translational regulation is crucial for understanding cellular function and drug development.A key molecule in protein translation is ribosome,which is a super-molecular complex extensively studied for more than a half century.The structure and dynamics of ribosome complexes were resolved recently thanks to the development of X-ray crystallography,Cryo-EM,and single molecule biophysics.Current studies of the ribosome have shown multiple functional states,each with a unique conformation.In this study,we analyzed the RNA-protein distances of ribosome(2.5 MDa)complexes and compared these changes among different ribosome complexes.We found that the RNA-protein distance is significantly correlated with the ribosomal functional state.Thus,the analysis of RNA-protein binding distances at important functional sites can distinguish ribosomal functional states and help understand ribosome functions.In particular,the mechanism of translational attenuation by nascent peptides and antibiotics was revealed by the conformational changes of local functional sites.展开更多
基金Supported by Funds of Natural Science of Shaanxi Education, No.05JK176Natural Science of Shaanxi Province, No.2010JM4023Natural Science of Xianyang City, No. 2010K14-02(6)
文摘AIM:To study the effect of breviscapine (Bre) on activity of protein kinase Cα (PKCα) and nuclear factor (NF)-κB in pancreas,and the mechanism of Bre attenuating acute pancreatitis (AP). METHODS:One hundred and eight rats were randomly divided into acute necrotizing pancreatitis (ANP) group,Bre group (ANP + Bre group) and sham operation (SO) group,36 rats in each group. ANP model was induced by a retrograde injection of 4% sodium deoxycholate into the bilio-pancreatic duct. Fifteen minutes after the ANP model was induced,the rats in Bre group were intraperitoneally injected with Bre (0.4 mg/100 g body weight or 0.1 mL/100 g body weight). Survival time and mortality of rats were calculated. Serum amylase and malondialdehyde levels were measured,volume of ascites was recorded and morphology of pancreas and lung was evaluated at 1,5 and 10 h,after the ANP model was induced,respectively. Expressions of PKCα and subunit p65 of NF-κB in pancreas were detected by immunohistochemistry and Western blotting. RESULTS:The life span of rats was longer and the mortality was lower in Bre group than in ANP group 13.51 ± 5.46 vs 25.36 ± 8.11 (P < 0.05). The amylase and MDA levels as well as the volume of ascites were lower and the pathological changes in pancreas and lung were less in Bre group than ANP group (P < 0.05),indicating that the pancreatitis is less severe in Bre group than ANP group. The activation of PKCα and NF-κB p65 in pancreas was induced rapidly and reached their peak at 1 h or 5 h after ANP,but their activity in Bre group was significantly inhibited. CONCLUSION:Bre exerts its therapeutic effect on AP by inhibiting the activation of PKCα and NF-κB p65 in pancreas.
基金partially supported by National Institute of Health(R21/R33-GM078601 and R01-GM100701)National Science Foundation(MCB-1151343)in the US
文摘Elucidating protein translational regulation is crucial for understanding cellular function and drug development.A key molecule in protein translation is ribosome,which is a super-molecular complex extensively studied for more than a half century.The structure and dynamics of ribosome complexes were resolved recently thanks to the development of X-ray crystallography,Cryo-EM,and single molecule biophysics.Current studies of the ribosome have shown multiple functional states,each with a unique conformation.In this study,we analyzed the RNA-protein distances of ribosome(2.5 MDa)complexes and compared these changes among different ribosome complexes.We found that the RNA-protein distance is significantly correlated with the ribosomal functional state.Thus,the analysis of RNA-protein binding distances at important functional sites can distinguish ribosomal functional states and help understand ribosome functions.In particular,the mechanism of translational attenuation by nascent peptides and antibiotics was revealed by the conformational changes of local functional sites.
