BACKGROUND:The specificity in discriminating pancreatitis is limited in the positron emission tomography(PET)using Fluorine-18-fluorodeoxyglucose.Furthermore,PET is not widely available compared to the single photon e...BACKGROUND:The specificity in discriminating pancreatitis is limited in the positron emission tomography(PET)using Fluorine-18-fluorodeoxyglucose.Furthermore,PET is not widely available compared to the single photon emission computed tomography(SPECT).Since amino acids play a minor role in metabolism of inflammatory cells,the potential of the SPECT tracer,3-[ 123 I]iodo-L-α-methyltyrosine(123I-IMT),for detecting pancreatic cancer was examined in xenotransplantation models of human pancreatic carcinoma in mice. METHODS: 123 I-IMT was injected to eight mice inoculated with subcutaneous or orthotopic pancreatic tumors.Fused high-resolution-micro-SPECT(Hi-SPECT)and magnetic resonance imaging were performed.The gene expression level of L amino acid transport-system 1(LAT1)was analyzed and correlated with tumor uptake of 123 I-IMT. RESULTS:A high uptake of 123 I-IMT was detected in all tumor-bearing mice.The median tumor-to-background ratio (T/B)was 12.1(2.0-13.2)for orthotopic and 8.4(1.8-11.1)for subcutaneous xenotransplantation,respectively.Accordingly, the LAT1 expression in transplanted Colo357 cells was increased compared to non-malignant controls.CONCLUSIONS:Our mouse model could show a high 123 I-IMT uptake in pancreatic cancer.Fused MRI scans facilitate precise evaluation of uptake in the specific regions of interest.Further studies are required to confirm these findings in tumors derived from other human pancreatic cancer cells.Since amino acids play a minor role in the metabolism of inflammatory cells,the potential for application of 123 I-IMT to distinguish pancreatic tumor from inflammatory pancreatitis warrants further investigation.展开更多
Glutamate is a regulated molecule in the mammalian testis. Extracellular regulation of glutamate in the body is determined largely by the expression of plasmalemmal glutamate transporters. We have examined by PCR, wes...Glutamate is a regulated molecule in the mammalian testis. Extracellular regulation of glutamate in the body is determined largely by the expression of plasmalemmal glutamate transporters. We have examined by PCR, western blotting and immunocytochemistry the expression of a panel of sodium-dependent plasmalemmal glutamate transporters in the rat testis. Proteins examined included： glutamate aspartate transporter （GLAST）, glutamate transporter 1 （GLT1）, excitatory amino acid carrier 1 （EAAC1）, excitatory amino acid transporter 4 （EAAT4） and EAAT5. We demonstrate that many of the glutamate transporters in the testis are alternately spliced. GLAST is present as exon-3- and exon-9-skipping forms. GLT1 was similarly present as the alternately spliced forms GLT1 b and GLTlc, whereas the abundant brain form （GLTla） was detectable only at the mRNA level. EAAT5 was also strongly expressed, whereas EAAC1 and EAAT4 were absent. These patterns of expression were compared with the patterns of endogenous glutamate localization and with patterns of D-aspartate accumulation, as assessed by immunocytochemistry. The presence of multiple glutamate transporters in the testis, including unusually spliced forms, suggests that glutamate homeostasis may be critical in this organ. The apparent presence of many of these transporters in the testis and sperm may indicate a need for glutamate transport by such cells.展开更多
The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and...The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis Expression of glutamate-aspartate transporter remained unchanged at 6 hours 7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.展开更多
Amino acids are important substances that must be transported to tissues such as the brain and muscles. The process is considered insulin dependent. It is not known whether all the amino acids are almost equally depen...Amino acids are important substances that must be transported to tissues such as the brain and muscles. The process is considered insulin dependent. It is not known whether all the amino acids are almost equally dependent in their transportation to tissues. We want to know whether some important amino acids are transported differently from other amino acids. Especially tryptophan is important because it is converted to serotonin, melatonin or kynurenine. Results showed that Amino acids levels in the plasma were measured after the intakes of 50 grams of glucose or sucrose to young (18 - 22 years old) and old (≥50 years old) men. Total amino acids in the plasma decreased after the intakes of glucose. Total amino acids levels decreased more significantly in old men after the administration of sucrose. Total and non-essential amino acids in the plasma decreased significantly at 120 min after the intakes of glucose in young and old men, but only sucrose caused their decreases in both aged and young men. Both glucose and sucrose intakes decreased significantly the plasma levels of the total essential and branched amino acids in young and old men. Surprisingly, plasma levels of tryptophan did not decrease upon the administration of glucose but only slightly decreased upon the administration of sucrose in young men. In conclusion, not all the amino acids were transported well into tissues upon the administration of glucose or sucrose. Tryptophan seems to be relatively resistant for insulin to facilitate the transportation into tissues.展开更多
目的:研究自发性癫痫大鼠皮质、海马中谷氨酸转运体-1(GLT-1)、兴奋性氨基酸载体-1(EAAC-1)的转录、表达水平及其意义。方法:选取自发性癫痫Wistar大鼠(癫痫组)和正常Wistar大鼠(正常组)各10只,采用反转录-聚合酶链式反应(RT-PCR)技术检...目的:研究自发性癫痫大鼠皮质、海马中谷氨酸转运体-1(GLT-1)、兴奋性氨基酸载体-1(EAAC-1)的转录、表达水平及其意义。方法:选取自发性癫痫Wistar大鼠(癫痫组)和正常Wistar大鼠(正常组)各10只,采用反转录-聚合酶链式反应(RT-PCR)技术检测2组大鼠皮质、海马中GLT-1、EAAC1 m RNA转录水平,采用蛋白质印迹技术检测2组大鼠皮质、海马中GLT-1、EAAC-1蛋白的表达水平。结果:癫痫组大鼠皮质中EAAC-1 m RNA相对灰度值为(0.67±0.21),明显低于正常组大鼠的(1.54±0.38)(P<0.01);2组大鼠皮质中GLT-1 m RNA和海马中GLT-1 m RNA、EAAC-1 m RNA相对灰度值差异无统计学意义(P>0.05)。癫痫组大鼠皮质中EAAC-1、GLT-1蛋白表达水平的相对灰度值分别为(72.6±8.7)和(103.7±12.6),显著低于正常组大鼠的(116.5±15.1)和(139.5±14.2)(P<0.01);癫痫组大鼠海马中GLT-1蛋白表达水平的相对灰度值(196.7±23.5)明显的高于正常组大鼠的(145.5±19.7)(P<0.01);2组大鼠海马中EAAC-1蛋白表达水平的相对灰度值差异无统计学意义(P>0.05)。结论:自发性癫痫大鼠皮质中GLT-1、EAAC-1表达水平下调可能与癫痫发生有关。展开更多
基金supported in part by a BMBF grant(TOMCAT)given to H.K.the Molecular Imaging North Competence Center(MOIN-CC)
文摘BACKGROUND:The specificity in discriminating pancreatitis is limited in the positron emission tomography(PET)using Fluorine-18-fluorodeoxyglucose.Furthermore,PET is not widely available compared to the single photon emission computed tomography(SPECT).Since amino acids play a minor role in metabolism of inflammatory cells,the potential of the SPECT tracer,3-[ 123 I]iodo-L-α-methyltyrosine(123I-IMT),for detecting pancreatic cancer was examined in xenotransplantation models of human pancreatic carcinoma in mice. METHODS: 123 I-IMT was injected to eight mice inoculated with subcutaneous or orthotopic pancreatic tumors.Fused high-resolution-micro-SPECT(Hi-SPECT)and magnetic resonance imaging were performed.The gene expression level of L amino acid transport-system 1(LAT1)was analyzed and correlated with tumor uptake of 123 I-IMT. RESULTS:A high uptake of 123 I-IMT was detected in all tumor-bearing mice.The median tumor-to-background ratio (T/B)was 12.1(2.0-13.2)for orthotopic and 8.4(1.8-11.1)for subcutaneous xenotransplantation,respectively.Accordingly, the LAT1 expression in transplanted Colo357 cells was increased compared to non-malignant controls.CONCLUSIONS:Our mouse model could show a high 123 I-IMT uptake in pancreatic cancer.Fused MRI scans facilitate precise evaluation of uptake in the specific regions of interest.Further studies are required to confirm these findings in tumors derived from other human pancreatic cancer cells.Since amino acids play a minor role in the metabolism of inflammatory cells,the potential for application of 123 I-IMT to distinguish pancreatic tumor from inflammatory pancreatitis warrants further investigation.
文摘Glutamate is a regulated molecule in the mammalian testis. Extracellular regulation of glutamate in the body is determined largely by the expression of plasmalemmal glutamate transporters. We have examined by PCR, western blotting and immunocytochemistry the expression of a panel of sodium-dependent plasmalemmal glutamate transporters in the rat testis. Proteins examined included： glutamate aspartate transporter （GLAST）, glutamate transporter 1 （GLT1）, excitatory amino acid carrier 1 （EAAC1）, excitatory amino acid transporter 4 （EAAT4） and EAAT5. We demonstrate that many of the glutamate transporters in the testis are alternately spliced. GLAST is present as exon-3- and exon-9-skipping forms. GLT1 was similarly present as the alternately spliced forms GLT1 b and GLTlc, whereas the abundant brain form （GLTla） was detectable only at the mRNA level. EAAT5 was also strongly expressed, whereas EAAC1 and EAAT4 were absent. These patterns of expression were compared with the patterns of endogenous glutamate localization and with patterns of D-aspartate accumulation, as assessed by immunocytochemistry. The presence of multiple glutamate transporters in the testis, including unusually spliced forms, suggests that glutamate homeostasis may be critical in this organ. The apparent presence of many of these transporters in the testis and sperm may indicate a need for glutamate transport by such cells.
基金supported by the National Natural Science Foundation of China, No. 81171168Shanghai Science and Technology Committee, No. 10140903200
文摘The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis Expression of glutamate-aspartate transporter remained unchanged at 6 hours 7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.
文摘Amino acids are important substances that must be transported to tissues such as the brain and muscles. The process is considered insulin dependent. It is not known whether all the amino acids are almost equally dependent in their transportation to tissues. We want to know whether some important amino acids are transported differently from other amino acids. Especially tryptophan is important because it is converted to serotonin, melatonin or kynurenine. Results showed that Amino acids levels in the plasma were measured after the intakes of 50 grams of glucose or sucrose to young (18 - 22 years old) and old (≥50 years old) men. Total amino acids in the plasma decreased after the intakes of glucose. Total amino acids levels decreased more significantly in old men after the administration of sucrose. Total and non-essential amino acids in the plasma decreased significantly at 120 min after the intakes of glucose in young and old men, but only sucrose caused their decreases in both aged and young men. Both glucose and sucrose intakes decreased significantly the plasma levels of the total essential and branched amino acids in young and old men. Surprisingly, plasma levels of tryptophan did not decrease upon the administration of glucose but only slightly decreased upon the administration of sucrose in young men. In conclusion, not all the amino acids were transported well into tissues upon the administration of glucose or sucrose. Tryptophan seems to be relatively resistant for insulin to facilitate the transportation into tissues.
基金This work was supported by grants from National Natural Science Foundation of China ( No. 39825109) and National Key Project of Basic Science Research (No. G1999054007).
文摘目的:研究自发性癫痫大鼠皮质、海马中谷氨酸转运体-1(GLT-1)、兴奋性氨基酸载体-1(EAAC-1)的转录、表达水平及其意义。方法:选取自发性癫痫Wistar大鼠(癫痫组)和正常Wistar大鼠(正常组)各10只,采用反转录-聚合酶链式反应(RT-PCR)技术检测2组大鼠皮质、海马中GLT-1、EAAC1 m RNA转录水平,采用蛋白质印迹技术检测2组大鼠皮质、海马中GLT-1、EAAC-1蛋白的表达水平。结果:癫痫组大鼠皮质中EAAC-1 m RNA相对灰度值为(0.67±0.21),明显低于正常组大鼠的(1.54±0.38)(P<0.01);2组大鼠皮质中GLT-1 m RNA和海马中GLT-1 m RNA、EAAC-1 m RNA相对灰度值差异无统计学意义(P>0.05)。癫痫组大鼠皮质中EAAC-1、GLT-1蛋白表达水平的相对灰度值分别为(72.6±8.7)和(103.7±12.6),显著低于正常组大鼠的(116.5±15.1)和(139.5±14.2)(P<0.01);癫痫组大鼠海马中GLT-1蛋白表达水平的相对灰度值(196.7±23.5)明显的高于正常组大鼠的(145.5±19.7)(P<0.01);2组大鼠海马中EAAC-1蛋白表达水平的相对灰度值差异无统计学意义(P>0.05)。结论:自发性癫痫大鼠皮质中GLT-1、EAAC-1表达水平下调可能与癫痫发生有关。
