Activation of metabotropic glutamate receptor la aggravates traumatic brain injury. The constitutively expressed protein Homerlb/c participates in delivering and anchoring metabotropic glutamate receptors in neurons. ...Activation of metabotropic glutamate receptor la aggravates traumatic brain injury. The constitutively expressed protein Homerlb/c participates in delivering and anchoring metabotropic glutamate receptors in neurons. Here, we aimed to verify whether down-regulation of Homerlb/c by RNA interference could protect cultured rat cortical neurons from traumatic injury. We showed that 36 hours after transfection of Homerlb/c small interfering RNA, metabotropic glutamate receptor la was present only in the neuronal cytoplasm, but not in the dendrites. Calcium fluorescence intensity was also decreased significantly. Moreover, lactate dehydrogenase concentration was significantly decreased in Homerlb/c small interfering RNA-transfected cells compared with that in untransfected and control small interfering RNA-transfected cells 24 hours after traumatic neuronal injury. Our findings indicate that down-regulation of Homerlb/c could reduce metabotropic glutamate receptor la transfer from the cell body to the dendrite, relieve calcium overload, and protect neurons from traumatic injury.展开更多
3-Bromopyruvate(3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase(LDH), 3BP also se...3-Bromopyruvate(3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase(LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells(oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione(GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level(4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions(1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow展开更多
The catalytic activity of two common bacterial enzymes, lactate dehydrogenase （LDH） and cytochrome c oxidase （COX） from Escherichia coli was examined following bacterial exposure to microwave （MW） radiation unde...The catalytic activity of two common bacterial enzymes, lactate dehydrogenase （LDH） and cytochrome c oxidase （COX） from Escherichia coli was examined following bacterial exposure to microwave （MW） radiation under well-defined experimental conditions. The experiments were conducted in a specialized microwave processing apparatus, with an exposure frequency of 18 GHz, and a temperature profile that was restricted to below 40℃ to avoid thermal degradation of the bacteria. The absorbed power was calculated to be 1,500 kW/m3 and the electric field was determined to be 300 Wm. Both values were theoretically confirmed using Computer Simulation Technology （CST） Microwave Studio 3D Electromagnetic Stimulation Software. Results showed that the activity of both enzymes was increased following MW radiation compared to negative controls and thermally treated samples subjected to similar temperature profiles. It is suggested that the increase in COX and LDH enzyme activity could not be explained by conventional heating alone, but was rather a result of micro-thermal effects that incorporated ＇undetectable＇ thermal mechanisms.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.31040011,31260512 and 30960054)the Key Science and Technology Project of Ministry of Education,China(No.209132)
基金supported by the National Natural Science Foundation of China, No. 30930093the Natural Science Foundation of Shaanxi Province, No. 2005C_245
文摘Activation of metabotropic glutamate receptor la aggravates traumatic brain injury. The constitutively expressed protein Homerlb/c participates in delivering and anchoring metabotropic glutamate receptors in neurons. Here, we aimed to verify whether down-regulation of Homerlb/c by RNA interference could protect cultured rat cortical neurons from traumatic injury. We showed that 36 hours after transfection of Homerlb/c small interfering RNA, metabotropic glutamate receptor la was present only in the neuronal cytoplasm, but not in the dendrites. Calcium fluorescence intensity was also decreased significantly. Moreover, lactate dehydrogenase concentration was significantly decreased in Homerlb/c small interfering RNA-transfected cells compared with that in untransfected and control small interfering RNA-transfected cells 24 hours after traumatic neuronal injury. Our findings indicate that down-regulation of Homerlb/c could reduce metabotropic glutamate receptor la transfer from the cell body to the dendrite, relieve calcium overload, and protect neurons from traumatic injury.
文摘3-Bromopyruvate(3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase(LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells(oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione(GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level(4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions(1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow
文摘The catalytic activity of two common bacterial enzymes, lactate dehydrogenase （LDH） and cytochrome c oxidase （COX） from Escherichia coli was examined following bacterial exposure to microwave （MW） radiation under well-defined experimental conditions. The experiments were conducted in a specialized microwave processing apparatus, with an exposure frequency of 18 GHz, and a temperature profile that was restricted to below 40℃ to avoid thermal degradation of the bacteria. The absorbed power was calculated to be 1,500 kW/m3 and the electric field was determined to be 300 Wm. Both values were theoretically confirmed using Computer Simulation Technology （CST） Microwave Studio 3D Electromagnetic Stimulation Software. Results showed that the activity of both enzymes was increased following MW radiation compared to negative controls and thermally treated samples subjected to similar temperature profiles. It is suggested that the increase in COX and LDH enzyme activity could not be explained by conventional heating alone, but was rather a result of micro-thermal effects that incorporated ＇undetectable＇ thermal mechanisms.
