The effect of change in concentration of messenger molecule inositol 1,4,5-trisphosphate (IP3) on intracellular Ca^2+spiral pattern evolution is studied numerically. The results indicate that when the IP3 concentra...The effect of change in concentration of messenger molecule inositol 1,4,5-trisphosphate (IP3) on intracellular Ca^2+spiral pattern evolution is studied numerically. The results indicate that when the IP3 concentration decreases from 0.27 μM, a physiologically reasonable value, to different values, the spiral centre drifts to the edge of the medium and disappears for a small enough IP3 concentration. The instability of spiral pattern can be understood in terms of excitability-change controlled by the IP3 concentration. On the other hand, when the IP3 concentration increases from 0.27 μM, a homogeneous area with a high Ca^2+ concentration emerges and competes with the spiral pattern. A high enough IP3 concentration can lead the homogeneous area to occupy the whole medium. The instability of spiral pattern is ascribed to the change in stability of a stationary state with a high Ca^2+ concentration.展开更多
Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left a...Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.展开更多
The role of inositol 1,4,5-trisphosphate (IP3) in transducing heat-shock (HS) signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level r...The role of inositol 1,4,5-trisphosphate (IP3) in transducing heat-shock (HS) signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase (GUS) fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C (PLC) inhibitors {1-[6-(( 1713-3-Methoxyestra-1,3,5(10)-trien- 7-yl)amino)hexyl]-2,5-pyrrolidinedione } (U-73122). The intracellular-free calcium ion concentration ([Ca^2+]i) increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2+]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.展开更多
The present study aims to explore the effects of p53 and its target gene Rap2B on the autophagy of U2OS cells.U2OS cells were treated with siRNA against p53,Rap2B,and PLCε.Relative expressions of p53,Rap2B,and PLCεw...The present study aims to explore the effects of p53 and its target gene Rap2B on the autophagy of U2OS cells.U2OS cells were treated with siRNA against p53,Rap2B,and PLCε.Relative expressions of p53,Rap2B,and PLCεwere determined using quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.Levels of IP3 in the cells were determined using Enzyme-linked Immunosorbent Assay(ELISA).Levels of Ca^(2+) were detected using Flow cytometry.Fluorescence microscopy was used to observe the autophagy of cells.Knockdown of p53 significantly decreased the expressions of Rap2B protein.Additionally,knockdown of p53 significantly decreased the mRNA levels of PLCε.The knockdown of p53,Rap2B,and PLCεsignificantly decreased the levels of intracellular IP3 and Ca^(2+) and promoted autophagy of U2OS cells.Our results demonstrated that p53-Rap2B-PLCε-IP3 signaling pathway regulated autophagy of U2OS cells.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant Nos 10575041 and 10747005)
文摘The effect of change in concentration of messenger molecule inositol 1,4,5-trisphosphate (IP3) on intracellular Ca^2+spiral pattern evolution is studied numerically. The results indicate that when the IP3 concentration decreases from 0.27 μM, a physiologically reasonable value, to different values, the spiral centre drifts to the edge of the medium and disappears for a small enough IP3 concentration. The instability of spiral pattern can be understood in terms of excitability-change controlled by the IP3 concentration. On the other hand, when the IP3 concentration increases from 0.27 μM, a homogeneous area with a high Ca^2+ concentration emerges and competes with the spiral pattern. A high enough IP3 concentration can lead the homogeneous area to occupy the whole medium. The instability of spiral pattern is ascribed to the change in stability of a stationary state with a high Ca^2+ concentration.
基金This study was supported by Beijing University of Traditional Chinese Medicine Dongzhimen Hospital 2022 Science and Technology Innovation Special Project(DZMKJCX-2022-008)。
文摘Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.
基金This work was supported by the National Natural Science Foundation of China (No. 30270796) Natural Science Foundation of Hebei Province, China (No. C2005000171).
文摘The role of inositol 1,4,5-trisphosphate (IP3) in transducing heat-shock (HS) signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase (GUS) fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C (PLC) inhibitors {1-[6-(( 1713-3-Methoxyestra-1,3,5(10)-trien- 7-yl)amino)hexyl]-2,5-pyrrolidinedione } (U-73122). The intracellular-free calcium ion concentration ([Ca^2+]i) increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2+]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.
文摘The present study aims to explore the effects of p53 and its target gene Rap2B on the autophagy of U2OS cells.U2OS cells were treated with siRNA against p53,Rap2B,and PLCε.Relative expressions of p53,Rap2B,and PLCεwere determined using quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.Levels of IP3 in the cells were determined using Enzyme-linked Immunosorbent Assay(ELISA).Levels of Ca^(2+) were detected using Flow cytometry.Fluorescence microscopy was used to observe the autophagy of cells.Knockdown of p53 significantly decreased the expressions of Rap2B protein.Additionally,knockdown of p53 significantly decreased the mRNA levels of PLCε.The knockdown of p53,Rap2B,and PLCεsignificantly decreased the levels of intracellular IP3 and Ca^(2+) and promoted autophagy of U2OS cells.Our results demonstrated that p53-Rap2B-PLCε-IP3 signaling pathway regulated autophagy of U2OS cells.