BACKGROUND： Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2＋. Zn^2＋ metabolism in the mossy fiber pathway, and Zn^2＋ accumulation in presy...BACKGROUND： Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2＋. Zn^2＋ metabolism in the mossy fiber pathway, and Zn^2＋ accumulation in presynaptic membrane vesicles, are dependent on zinc transporter 1 （ZnT1） and glutamate receptor subunit 2 （GluR2）. OBJECTIVE： To investigate the effects of long-term recurrent neonatal seizure, in the presence and absence of physical exercise, on the developmental expression of hippocampal zinc transporter 1 （ZnT1） and GluR2, and on cognitive function in rats. DESIGN, TIME AND SETTING： Based on behavioral examination and molecular biological research, a randomized, controlled animal experiment was performed at the Department of Neurobiology, Medical College of Soochow University, between January 2007 and April 2008. MATERIALS： Twenty-one 6-day-old Sprague Dawley rats of either gender were employed in this study. ZnT1 mRNA in situ hybridization kit was provided by Tianjin Haoyang Biological Manufacture Co.,Ltd., China. Rabbit anti-GluR2 was purchased from Santa Cruz Biotech, Inc, USA. METHODS： Rats were randomly divided into a recurrent seizure group （n = 11） and a control group （n = 10）. In the recurrent seizure group, 30-minute seizure was induced by flurothyl gas inhalation for a total of 6 consecutive days. Rats from the control group underwent experimental procedures similar to the recurrent seizure group, with the exception of flurothyl gas inhalation. Thirty minutes of treadmill exercise was performed daily by all rats at postnatal days 51–56. MAIN OUTCOME MEASURES： At postnatal day 82, rat hippocampal tissue was harvested for analysis of hippocampal ZnT1 and GluR2 expression by in situ hybridization and immunohistochemistry, respectively. Rat learning and memory capabilities were examined using the Y-maze test. RESULTS： In the recurrent seizure group, the gray scale value of ZnT1 in situ hybridization positive neurons in the hippocampal CA3 region was significantly greater （P 〈 0.05）, while the gray scale value of GluR2 immunoreactive neurons in the hippocampal hilus and dentate gyrus was significantly lower （P 〈 0.05）, than in the control group. At postnatal days 29–35, numbers of trials to criteria for successful learning were greater in the recurrent seizure group than in the control group （P 〈 0.05）; at postnatal days 61–67, the numbers of trials to criteria for successful learning were similar between the two groups （P 〉 0.05）. At postnatal days 29–35 and 61–67, there was no significant difference in memory capability between the recurrent seizure and control groups （P 〉 0.05）. CONCLUSION： Physical exercise likely improves the learning deficits caused by recurrent neonatal seizure in rats during brain development by modulating ZnT1 and GluR2 expression.展开更多
LIV-1(solute carrier family 39 member 6,SLC39A6/ZIP6)是锌转运蛋白ZIP家族中LZT(LIV-1 subfamily of ZIP zinc Transporters)亚家族成员之一,定位于细胞膜,富含组氨酸,并包含有多个跨膜结构域,主要分布于受激素调控的组织中。LIV-1...LIV-1(solute carrier family 39 member 6,SLC39A6/ZIP6)是锌转运蛋白ZIP家族中LZT(LIV-1 subfamily of ZIP zinc Transporters)亚家族成员之一,定位于细胞膜,富含组氨酸,并包含有多个跨膜结构域,主要分布于受激素调控的组织中。LIV-1的主要功能是将Zn2+转运至细胞质基质中从而提高基质内Zn2+的含量,此外研究表明,LIV-1还参与胚胎发育以及肿瘤迁移中所涉及的上皮-间充质细胞转化过程(epithelial-to-mesenchymal transition,EMT),提示除与锌离子运输外,它可能与肿瘤等多种疾病的发生发展也有着密切地联系。本文将对锌转运蛋白LIV-1的相关研究进展进行综述。展开更多
BACKGROUND： Autophagy is a homeostatic process for intracellular recycling of bulk proteins and aging organelles. Increased autophagy has now been reported in experimental models of traumatic brain injury, stroke and...BACKGROUND： Autophagy is a homeostatic process for intracellular recycling of bulk proteins and aging organelles. Increased autophagy has now been reported in experimental models of traumatic brain injury, stroke and excitotoxicity, and in patients with Alzheimer＇s disease and critical illness. The role of autophagy in developmental epilepsy, however, is unknown. The present study was to investigate the effects of recurrent neonatal seizure, in the presence and absence of autophagy inhibitor 3-methyladenine （3-MA）, on the acute phase gene expression of ZnTs, LC3 and Beclin-1 in rat cerebral cortex and the interaction among them.METHODS： Thirty-six Sprague-Dawley neonatal rats at postnatal day 6（P6） were randomly divided into three groups： a recurrent-seizures group （RS, n=12）, a 3-MA treated-seizure group （3-MA group, each rat pretreated with 3-methyladenine before seizures, 100nmol/μl/day, i.p., n=12） and a control group （n=12）. At 1.5 and 6 hours after the last seizures, the mRNA levels of ZnT1-ZnT3, microtubule-associated protein 1A/1B light chain 3 （LC3） and beclin-1 were detected using the real-time RT-PCR method. The LC3 protein level was examined by Western blotting.RESULTS： The levels of LC3, beclin-1 and ZnT-2 transcripts in the RS group elevated signi？ cantly at 1.5 and 6 hours after the last seizures compared with those in the control and 3-MA groups. At the interval of 1.5 hours, the mRNA level of ZnT-1 increased signi？ cantly after the last seizure compared with that in the control group. There was no signi？ cant difference in the transcript levels of ZnT-3 among the three groups. Linear correlation analysis showed that the expression of the ？ ve genes in the control group exhibited a signi？ cant inter-relationship. In the 3-MA group, however, the inter-relationship was only found between beclin-1 and ZnT-1. In the RS group, the inter-relationship was not observed.CONCLUSIONS： The autophagy/lysosomal pathway is immediately activated along with the elevated expression of ZnT1 and ZnT2 in the cerebral cortex after recurrent seizures. 3-MA is involved in the regulation of the autophagy/lysosomal pathway and ZnTs by down-regulating the expression of LC3 and beclin-1.展开更多
Objective： To evaluate the utility of zinc transporter-8 （ZnT8） in the improvement of type 1 diabetes mellitus （T1DM） diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in TI ...Objective： To evaluate the utility of zinc transporter-8 （ZnT8） in the improvement of type 1 diabetes mellitus （T1DM） diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in TI DM. Data Sources： A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows： ＂ZnTS,＂ ＂type 1 diabetes,＂ ＂latent autoimmune diabetes in adults,＂ ＂type 2 diabetes,＂ ＂islet autoantibodies,＂ ＂zinc supplement,＂ ＂T cells,＂ ＂[3 cell,＂ ＂immune therapy.＂ We also searched the reference lists of selected articles. Study Selection： English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed. Results： The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 （ZnTSA） and ZnTS-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy. Conclusions： ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.展开更多
基金the National Natural Science Foundation of China, No. 30470555, 30571909, 30870808the Natural Science Foundation of Jiangsu Province, No. BK2007509Natural Science Foundation for Colleges and Universities in Jiangsu Province, No. 07KJB320103
文摘BACKGROUND： Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2＋. Zn^2＋ metabolism in the mossy fiber pathway, and Zn^2＋ accumulation in presynaptic membrane vesicles, are dependent on zinc transporter 1 （ZnT1） and glutamate receptor subunit 2 （GluR2）. OBJECTIVE： To investigate the effects of long-term recurrent neonatal seizure, in the presence and absence of physical exercise, on the developmental expression of hippocampal zinc transporter 1 （ZnT1） and GluR2, and on cognitive function in rats. DESIGN, TIME AND SETTING： Based on behavioral examination and molecular biological research, a randomized, controlled animal experiment was performed at the Department of Neurobiology, Medical College of Soochow University, between January 2007 and April 2008. MATERIALS： Twenty-one 6-day-old Sprague Dawley rats of either gender were employed in this study. ZnT1 mRNA in situ hybridization kit was provided by Tianjin Haoyang Biological Manufacture Co.,Ltd., China. Rabbit anti-GluR2 was purchased from Santa Cruz Biotech, Inc, USA. METHODS： Rats were randomly divided into a recurrent seizure group （n = 11） and a control group （n = 10）. In the recurrent seizure group, 30-minute seizure was induced by flurothyl gas inhalation for a total of 6 consecutive days. Rats from the control group underwent experimental procedures similar to the recurrent seizure group, with the exception of flurothyl gas inhalation. Thirty minutes of treadmill exercise was performed daily by all rats at postnatal days 51–56. MAIN OUTCOME MEASURES： At postnatal day 82, rat hippocampal tissue was harvested for analysis of hippocampal ZnT1 and GluR2 expression by in situ hybridization and immunohistochemistry, respectively. Rat learning and memory capabilities were examined using the Y-maze test. RESULTS： In the recurrent seizure group, the gray scale value of ZnT1 in situ hybridization positive neurons in the hippocampal CA3 region was significantly greater （P 〈 0.05）, while the gray scale value of GluR2 immunoreactive neurons in the hippocampal hilus and dentate gyrus was significantly lower （P 〈 0.05）, than in the control group. At postnatal days 29–35, numbers of trials to criteria for successful learning were greater in the recurrent seizure group than in the control group （P 〈 0.05）; at postnatal days 61–67, the numbers of trials to criteria for successful learning were similar between the two groups （P 〉 0.05）. At postnatal days 29–35 and 61–67, there was no significant difference in memory capability between the recurrent seizure and control groups （P 〉 0.05）. CONCLUSION： Physical exercise likely improves the learning deficits caused by recurrent neonatal seizure in rats during brain development by modulating ZnT1 and GluR2 expression.
文摘LIV-1(solute carrier family 39 member 6,SLC39A6/ZIP6)是锌转运蛋白ZIP家族中LZT(LIV-1 subfamily of ZIP zinc Transporters)亚家族成员之一,定位于细胞膜,富含组氨酸,并包含有多个跨膜结构域,主要分布于受激素调控的组织中。LIV-1的主要功能是将Zn2+转运至细胞质基质中从而提高基质内Zn2+的含量,此外研究表明,LIV-1还参与胚胎发育以及肿瘤迁移中所涉及的上皮-间充质细胞转化过程(epithelial-to-mesenchymal transition,EMT),提示除与锌离子运输外,它可能与肿瘤等多种疾病的发生发展也有着密切地联系。本文将对锌转运蛋白LIV-1的相关研究进展进行综述。
文摘BACKGROUND： Autophagy is a homeostatic process for intracellular recycling of bulk proteins and aging organelles. Increased autophagy has now been reported in experimental models of traumatic brain injury, stroke and excitotoxicity, and in patients with Alzheimer＇s disease and critical illness. The role of autophagy in developmental epilepsy, however, is unknown. The present study was to investigate the effects of recurrent neonatal seizure, in the presence and absence of autophagy inhibitor 3-methyladenine （3-MA）, on the acute phase gene expression of ZnTs, LC3 and Beclin-1 in rat cerebral cortex and the interaction among them.METHODS： Thirty-six Sprague-Dawley neonatal rats at postnatal day 6（P6） were randomly divided into three groups： a recurrent-seizures group （RS, n=12）, a 3-MA treated-seizure group （3-MA group, each rat pretreated with 3-methyladenine before seizures, 100nmol/μl/day, i.p., n=12） and a control group （n=12）. At 1.5 and 6 hours after the last seizures, the mRNA levels of ZnT1-ZnT3, microtubule-associated protein 1A/1B light chain 3 （LC3） and beclin-1 were detected using the real-time RT-PCR method. The LC3 protein level was examined by Western blotting.RESULTS： The levels of LC3, beclin-1 and ZnT-2 transcripts in the RS group elevated signi？ cantly at 1.5 and 6 hours after the last seizures compared with those in the control and 3-MA groups. At the interval of 1.5 hours, the mRNA level of ZnT-1 increased signi？ cantly after the last seizure compared with that in the control group. There was no signi？ cant difference in the transcript levels of ZnT-3 among the three groups. Linear correlation analysis showed that the expression of the ？ ve genes in the control group exhibited a signi？ cant inter-relationship. In the 3-MA group, however, the inter-relationship was only found between beclin-1 and ZnT-1. In the RS group, the inter-relationship was not observed.CONCLUSIONS： The autophagy/lysosomal pathway is immediately activated along with the elevated expression of ZnT1 and ZnT2 in the cerebral cortex after recurrent seizures. 3-MA is involved in the regulation of the autophagy/lysosomal pathway and ZnTs by down-regulating the expression of LC3 and beclin-1.
文摘Objective： To evaluate the utility of zinc transporter-8 （ZnT8） in the improvement of type 1 diabetes mellitus （T1DM） diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in TI DM. Data Sources： A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows： ＂ZnTS,＂ ＂type 1 diabetes,＂ ＂latent autoimmune diabetes in adults,＂ ＂type 2 diabetes,＂ ＂islet autoantibodies,＂ ＂zinc supplement,＂ ＂T cells,＂ ＂[3 cell,＂ ＂immune therapy.＂ We also searched the reference lists of selected articles. Study Selection： English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed. Results： The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 （ZnTSA） and ZnTS-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy. Conclusions： ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.
