Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sou...Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sought to identify an anti-apoptotic mechanism for the treatment of neurodegenerative diseases. Primary cultured neurons were treated with different concentrations of rotenone for 48 hours. Morphological observation, cell counting kit-8 assay, lactate dehydrogenase detection and western blot assay demonstrated that 0.5 n M rotenone increased lactate dehydrogenase release, decreased the expression of procaspase-3 and Bcl-2, and increased cleaved caspase-3 expression in normal neurons. All these effects were prevented by geniposide. Our results indicate that geniposide diminished rotenone-induced injury in primary neurons by suppressing apoptosis. This may be one of the molecular mechanisms underlying the efficacy of geniposide in the treatment of neurodegenerative diseases.展开更多
Apoptosis of tumor cells have become a new standard for chemotherapy. It is useful to demonstrate induction of apoptosis in tumor cells by anti-cancer drugs in vivo. We reported the results of apoptosis induction in m...Apoptosis of tumor cells have become a new standard for chemotherapy. It is useful to demonstrate induction of apoptosis in tumor cells by anti-cancer drugs in vivo. We reported the results of apoptosis induction in murine tumor cell line S-180 and it's resistant cell line S-180R by adriamycin in different dose and different time. We found that apoptosis in S-180 cells could be induced by low dose of adriamycin, the apoptosis was started at 24 h. after the administration, and reached to 62.5% of the cells to apptosis until 72 h. Comparison with the parental cell line, only 13% of S-180R cells were apoptosed. At high dose, 20% of S-180R cells were apoptosed, whereas, almost all S-180 cells were killed in the same time. The lymphocytes were appeared in abdominal cavity of the mice after treatment of adriamycin for 24 h. It was very interested to find out that there was no lymphocyte left in the abdominal cavity of the mice with S-180R cells treated at high dose of adriamycin.展开更多
Objective: To investigate the gene regulation of taxolinduced apoptosis Methods: Northern blot hybridization, enzyme activity assay of S AdoMet synthetase and flow cytometry were performed in the investigation of ex...Objective: To investigate the gene regulation of taxolinduced apoptosis Methods: Northern blot hybridization, enzyme activity assay of S AdoMet synthetase and flow cytometry were performed in the investigation of expression in the mRNA level and biological action of S AdoMet synthetase in taxol induced apoptosis in human breast cancer cell line (BCap 37) Results: Up regulation of S AdoMet synthetase expression was resulted by taxol treatment and the expression peaked at 48 hours Moreover,the up regulation of S AdoMet synthetase was associated with cytotoxicity of anti microtubule agents including taxol and colchicine Inhibition rate of S AdoMet synthetase activity by 1% DMSO was 34% in taxol treated cells and 14% in taxol untreated cells compared to control groups, respectively Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hrs promoted apoptotic cell death of taxol ,colchicine ,and adriamycin treated Bcap37 cells Conclusion : The induction of apoptosis enhanced by post treatment with DMSO in taxol treated cells is probably linked to its inhibition on enzyme activity of S AdoMet synthetase ,suggesting that the increased expression of S AdoMet synthetase possibly plays an important role in protecting cells from DNA fragmentation in taxol induced apoptosis Accepted July 26, 1998 This work was supported by the National High Biotechnology Foundation of China and a grant from the Natural Science Foundation of Zhejiang Province, China展开更多
To study gene control mechanisms in Xenopus embryos, we analyzed polyamines, cloned SAMDC (S-adenosylmethionine decarboxylase), a key enzyme of polyamine metabolism, and microinjected its mRNA into Xenopus fertilized ...To study gene control mechanisms in Xenopus embryos, we analyzed polyamines, cloned SAMDC (S-adenosylmethionine decarboxylase), a key enzyme of polyamine metabolism, and microinjected its mRNA into Xenopus fertilized eggs. The microinjection induced a large increase in SAMDC activity, exhaustion of the substrate SAM (S-adenosylmethionine), and execution of apoptosis at the stage called midblastula transition (MBT). By tracing GFP (green fluorescence protein)-marked apoptotic cells, we reached a conclusion that the apoptosis provides pre-blastula embryos with a fail-safe mechanism of early development. We analyzed caspase mRNAs and found that caspase-9 and -3 mRNAs are maternal mRNA and activation of caspase-9 is one of the key steps for the execution of the apoptosis. We also found that over- expression of caspase-8, and in addition p53, a tumor suppressor protein, also induces apoptosis at MBT, just like the overexpression of SAMDC and caspase-9 does. The apoptosis induced by p53 was suppressed by Xdm-2, a negative regulator of p53, and by a peptide inhibitor and a dominant-negative type mutant of caspase-9, but not by those of caspase-8. By contrast, apoptosis induced by SAMDC was suppressed by peptide inhibitors and dominant-negative mutants of both caspase-9 and caspase-8, but not by Xdm-2. Unlike caspase-9 mRNA, caspase-8 mRNA was not a maternal mRNA, but newly expressed during cleavage stage (pre-MBT stage) only in embryos overexpressed with SAMDC. In SAMDC-induced apoptotic embryos activities to process procaspase-8 and procaspase-9 appeared, whereas in p53-induced apoptotic embryos only activity to process procaspase-9 appeared. Thus, Xenopus embryos have at least two pathways to execute the maternal program of apoptosis: One induced by SAMDC overexpression through activation of caspase-9 and do novo expression of caspase-8 gene, and the other induced by p53 overexpression through activation of caspase-9 but not caspase-8. In Xenopus embryos, it has long been believed that zygotic genes are silent until MBT, but results obtained with caspase-8 may provide a novel example of gene expression before MBT.展开更多
基金supported by grants from the Shanxi Science and Technology Department in China,No.2011081060Shanxi Scholarship Council of China,No.2011-44
文摘Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sought to identify an anti-apoptotic mechanism for the treatment of neurodegenerative diseases. Primary cultured neurons were treated with different concentrations of rotenone for 48 hours. Morphological observation, cell counting kit-8 assay, lactate dehydrogenase detection and western blot assay demonstrated that 0.5 n M rotenone increased lactate dehydrogenase release, decreased the expression of procaspase-3 and Bcl-2, and increased cleaved caspase-3 expression in normal neurons. All these effects were prevented by geniposide. Our results indicate that geniposide diminished rotenone-induced injury in primary neurons by suppressing apoptosis. This may be one of the molecular mechanisms underlying the efficacy of geniposide in the treatment of neurodegenerative diseases.
文摘Apoptosis of tumor cells have become a new standard for chemotherapy. It is useful to demonstrate induction of apoptosis in tumor cells by anti-cancer drugs in vivo. We reported the results of apoptosis induction in murine tumor cell line S-180 and it's resistant cell line S-180R by adriamycin in different dose and different time. We found that apoptosis in S-180 cells could be induced by low dose of adriamycin, the apoptosis was started at 24 h. after the administration, and reached to 62.5% of the cells to apptosis until 72 h. Comparison with the parental cell line, only 13% of S-180R cells were apoptosed. At high dose, 20% of S-180R cells were apoptosed, whereas, almost all S-180 cells were killed in the same time. The lymphocytes were appeared in abdominal cavity of the mice after treatment of adriamycin for 24 h. It was very interested to find out that there was no lymphocyte left in the abdominal cavity of the mice with S-180R cells treated at high dose of adriamycin.
文摘Objective: To investigate the gene regulation of taxolinduced apoptosis Methods: Northern blot hybridization, enzyme activity assay of S AdoMet synthetase and flow cytometry were performed in the investigation of expression in the mRNA level and biological action of S AdoMet synthetase in taxol induced apoptosis in human breast cancer cell line (BCap 37) Results: Up regulation of S AdoMet synthetase expression was resulted by taxol treatment and the expression peaked at 48 hours Moreover,the up regulation of S AdoMet synthetase was associated with cytotoxicity of anti microtubule agents including taxol and colchicine Inhibition rate of S AdoMet synthetase activity by 1% DMSO was 34% in taxol treated cells and 14% in taxol untreated cells compared to control groups, respectively Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hrs promoted apoptotic cell death of taxol ,colchicine ,and adriamycin treated Bcap37 cells Conclusion : The induction of apoptosis enhanced by post treatment with DMSO in taxol treated cells is probably linked to its inhibition on enzyme activity of S AdoMet synthetase ,suggesting that the increased expression of S AdoMet synthetase possibly plays an important role in protecting cells from DNA fragmentation in taxol induced apoptosis Accepted July 26, 1998 This work was supported by the National High Biotechnology Foundation of China and a grant from the Natural Science Foundation of Zhejiang Province, China
文摘To study gene control mechanisms in Xenopus embryos, we analyzed polyamines, cloned SAMDC (S-adenosylmethionine decarboxylase), a key enzyme of polyamine metabolism, and microinjected its mRNA into Xenopus fertilized eggs. The microinjection induced a large increase in SAMDC activity, exhaustion of the substrate SAM (S-adenosylmethionine), and execution of apoptosis at the stage called midblastula transition (MBT). By tracing GFP (green fluorescence protein)-marked apoptotic cells, we reached a conclusion that the apoptosis provides pre-blastula embryos with a fail-safe mechanism of early development. We analyzed caspase mRNAs and found that caspase-9 and -3 mRNAs are maternal mRNA and activation of caspase-9 is one of the key steps for the execution of the apoptosis. We also found that over- expression of caspase-8, and in addition p53, a tumor suppressor protein, also induces apoptosis at MBT, just like the overexpression of SAMDC and caspase-9 does. The apoptosis induced by p53 was suppressed by Xdm-2, a negative regulator of p53, and by a peptide inhibitor and a dominant-negative type mutant of caspase-9, but not by those of caspase-8. By contrast, apoptosis induced by SAMDC was suppressed by peptide inhibitors and dominant-negative mutants of both caspase-9 and caspase-8, but not by Xdm-2. Unlike caspase-9 mRNA, caspase-8 mRNA was not a maternal mRNA, but newly expressed during cleavage stage (pre-MBT stage) only in embryos overexpressed with SAMDC. In SAMDC-induced apoptotic embryos activities to process procaspase-8 and procaspase-9 appeared, whereas in p53-induced apoptotic embryos only activity to process procaspase-9 appeared. Thus, Xenopus embryos have at least two pathways to execute the maternal program of apoptosis: One induced by SAMDC overexpression through activation of caspase-9 and do novo expression of caspase-8 gene, and the other induced by p53 overexpression through activation of caspase-9 but not caspase-8. In Xenopus embryos, it has long been believed that zygotic genes are silent until MBT, but results obtained with caspase-8 may provide a novel example of gene expression before MBT.
