目的探究ether-a-go-go相关基因(ether-a-go-go related gene,ERG)通道在胰岛β-细胞中的作用。方法提取野生型(wild type,WT)与ERG基因敲除型(knockout,KO)小鼠胰岛β-细胞,利用全细胞膜片钳技术记录钾离子电流与动作电位,分析敲除ERG...目的探究ether-a-go-go相关基因(ether-a-go-go related gene,ERG)通道在胰岛β-细胞中的作用。方法提取野生型(wild type,WT)与ERG基因敲除型(knockout,KO)小鼠胰岛β-细胞,利用全细胞膜片钳技术记录钾离子电流与动作电位,分析敲除ERG基因后钾电流与动作电位的变化。对两组小鼠进行腹腔注射葡萄糖耐量实验,分析基因敲除后小鼠糖耐量的变化,探究ERG基因是否对体内血糖浓度有影响。结果在两组小鼠胰岛β-细胞中记录到的钾离子电流均呈现内向整流趋势,KO组钾离子电流明显减小,动作电位时程明显延长。动物实验中,KO组小鼠糖刺激2 h后血糖浓度较WT组显著降低。结论 ERG通道电流是胰岛β-细胞中钾离子电流的重要组成部分,可显著影响动作电位时程,进而影响体内血糖浓度。展开更多
AIM: To study the expression of ether à go-go (Eag1) potassium channel in colorectal cancer and the relation- ship between their expression and clinico-pathological features. METHODS: The expression levels of Eag...AIM: To study the expression of ether à go-go (Eag1) potassium channel in colorectal cancer and the relation- ship between their expression and clinico-pathological features. METHODS: The expression levels of Eag1 protein were determined in 76 cancer tissues with paired non- cancerous matched tissues as well as 9 colorectal adenoma tissues by immunohistochemistry. Eag1 mRNA expression was detected in 13 colorectal cancer tissues with paired non-cancerous matched tissues and 4 colorectal adenoma tissues as well as two colorectal cancer cell lines (LoVo and HT-29) by reverse transcription PCR. RESULTS: The frequency of positive expression of Eag1 protein was 76.3% (58/76) and Eag1 mRNA was 76.9% (10/13) in colorectal cancer tissue. Expression level of Eag1 protein was dependent on the tumor size, lymphatic node metastasis, other organ metastases and Dukes’ stage (P < 0.05), while not dependent on age, sex, site and degree of differentiation. Eag1 protein and mRNA were negative in normal colorectal tissue, and absolutely negative in colorectal adenomas except that one case was positively stained for Eag1 protein. CONCLUSION: Eag1 protein and mRNA are aberrantly expressed in colorectal cancer and occasionally expressed in colorectal adenoma. The high frequency of expression of Eag1 in tumors and the restriction of normal expression to the brain suggest the potential of this protein for diagnostic, prognostic and therapeutic purposes.展开更多
Objective: To observe the effect of matrine on human ether à go-go related gene (HERG) potassium channels expressed in Chinese hamster ovary (CHO) cells and investigate whether HERG channel is a new target o...Objective: To observe the effect of matrine on human ether à go-go related gene (HERG) potassium channels expressed in Chinese hamster ovary (CHO) cells and investigate whether HERG channel is a new target of the pharmacological effect of matrine on arrhythmia and tumor. Methods: HERG channel potassium current in CHO cell was recorded using whole-cell patch-clamp technique, and the influence of matrine on the current was explored. Results: Matrine inhibited HERG potassium current in a dose-dependent manner, and the 50% inhibitory concentration (IC50) was 411±23 μmol/L. Matrine had no significant effect on the activation kinetics, and mainly blocked HERG channels in their closed state. Conclusions: The blocking effect of matrine on HERG channels might be one of the mechanisms against arrythmias and tumors. Unlike most other blockers exerting blocking effect at the intracellular sites by entering the cell with the opening of HERG channel, matrine blocked HERG channels at the extracellular sites.展开更多
Objective To explore the expression of etheràgo-go1(Eag1)in human osteosarcoma and its molecular mechanisms of regulating the malignant phenotype of osteosarcoma.Methods The expression levels of Eag1 in osteosarc...Objective To explore the expression of etheràgo-go1(Eag1)in human osteosarcoma and its molecular mechanisms of regulating the malignant phenotype of osteosarcoma.Methods The expression levels of Eag1 in osteosarcoma cell lines and human osteosarcoma tissues were detected by reverse transcription polymerase chain reaction(RT-PCR),western blot analysis and immunohistochemistry.The small interfering RNA(siRNA)was展开更多
文摘AIM: To study the expression of ether à go-go (Eag1) potassium channel in colorectal cancer and the relation- ship between their expression and clinico-pathological features. METHODS: The expression levels of Eag1 protein were determined in 76 cancer tissues with paired non- cancerous matched tissues as well as 9 colorectal adenoma tissues by immunohistochemistry. Eag1 mRNA expression was detected in 13 colorectal cancer tissues with paired non-cancerous matched tissues and 4 colorectal adenoma tissues as well as two colorectal cancer cell lines (LoVo and HT-29) by reverse transcription PCR. RESULTS: The frequency of positive expression of Eag1 protein was 76.3% (58/76) and Eag1 mRNA was 76.9% (10/13) in colorectal cancer tissue. Expression level of Eag1 protein was dependent on the tumor size, lymphatic node metastasis, other organ metastases and Dukes’ stage (P < 0.05), while not dependent on age, sex, site and degree of differentiation. Eag1 protein and mRNA were negative in normal colorectal tissue, and absolutely negative in colorectal adenomas except that one case was positively stained for Eag1 protein. CONCLUSION: Eag1 protein and mRNA are aberrantly expressed in colorectal cancer and occasionally expressed in colorectal adenoma. The high frequency of expression of Eag1 in tumors and the restriction of normal expression to the brain suggest the potential of this protein for diagnostic, prognostic and therapeutic purposes.
基金Supported by Beijing Administration Bureau of Traditional Chinese Medicine (No. JZZ-312)
文摘Objective: To observe the effect of matrine on human ether à go-go related gene (HERG) potassium channels expressed in Chinese hamster ovary (CHO) cells and investigate whether HERG channel is a new target of the pharmacological effect of matrine on arrhythmia and tumor. Methods: HERG channel potassium current in CHO cell was recorded using whole-cell patch-clamp technique, and the influence of matrine on the current was explored. Results: Matrine inhibited HERG potassium current in a dose-dependent manner, and the 50% inhibitory concentration (IC50) was 411±23 μmol/L. Matrine had no significant effect on the activation kinetics, and mainly blocked HERG channels in their closed state. Conclusions: The blocking effect of matrine on HERG channels might be one of the mechanisms against arrythmias and tumors. Unlike most other blockers exerting blocking effect at the intracellular sites by entering the cell with the opening of HERG channel, matrine blocked HERG channels at the extracellular sites.
文摘Objective To explore the expression of etheràgo-go1(Eag1)in human osteosarcoma and its molecular mechanisms of regulating the malignant phenotype of osteosarcoma.Methods The expression levels of Eag1 in osteosarcoma cell lines and human osteosarcoma tissues were detected by reverse transcription polymerase chain reaction(RT-PCR),western blot analysis and immunohistochemistry.The small interfering RNA(siRNA)was