Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across dif...Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.展开更多
Rehmannia has been shown to be clinically effective in treating neurodegenerative diseases; however, the neuroprotective mechanisms remain unclear. In this study, we established a model of neurodegenerative disease us...Rehmannia has been shown to be clinically effective in treating neurodegenerative diseases; however, the neuroprotective mechanisms remain unclear. In this study, we established a model of neurodegenerative disease using PC12 cytotoxic injury induced by glutamate. The cells were treated with 20 mM glutamate in the absence or presence of water extracts of dried Rehmannia root of varying concentrations（70%, 50% and 30%）. The different concentrations of Rehmannia water extract significantly increased the activity of glutamate-injured cells, reduced the release of lactate dehydrogenase, inhibited apoptosis, increased the concentrations of NADH, NAD and ATP in cells, ameliorated mitochondrial membrane potential, and reduced the levels of light chain 3. Taken together, our findings demonstrate that Rehmannia water extracts exert a cytoprotective effect against glutamate-induced PC12 cell injury via energy metabolism-related pathways.展开更多
Glutamine and glutamate are major bioenergy substrates for normal and cancer cell growth.Cancer cells need more biofuel than normal tissues for energy supply,anti-oxidation activity and biomass production.Genes relate...Glutamine and glutamate are major bioenergy substrates for normal and cancer cell growth.Cancer cells need more biofuel than normal tissues for energy supply,anti-oxidation activity and biomass production.Genes related to metabolic chains in many cancers are somehow mutated,which makes cancer cells more glutamate dependent.Meanwhile,glutamate is an excitatory neurotransmitter for conducting signals through binding with different types of receptors in central neuron system.Interestingly,increasing evidences have shown involvement of glutamate signaling,guided through their receptors,in human malignancy.Dysregulation of glutamate transporters,such as excitatory amino acid transporter and cystine/glutamate antiporter system,also generates excessive extracellular glutamate,which in turn,activates glutamate receptors on cancer cells and results in malignant growth.These features make glutamate an attractive target for anti-cancer drug development with some glutamate targeted but blood brain barrier impermeable anti-psychosis drugs under consideration.We discussed the relevant progressions and drawbacks in this field herein.展开更多
Objective To study the effect of glutamate on metabolism, shifts in glycolysis and lactate release in rat astrocytes. Methods After 10 days, secondary cultured astrocytes were treated with 1 mmol/L glutamate for 1 h, ...Objective To study the effect of glutamate on metabolism, shifts in glycolysis and lactate release in rat astrocytes. Methods After 10 days, secondary cultured astrocytes were treated with 1 mmol/L glutamate for 1 h, and the oxygen consumption rates （OCR） and extra cellular acidification rate （ECAR） was analyzed using a Seahorse XF 24 Extracellular Flux Analyzer. Cell viability was then evaluated by MTT assay. Moreover, changes in extracellular lactate concentration induced by glutamate were tested with a lactate detection kit. Results Compared with the control group, treatment with 1 mmol/L glutamate decreased the astrocytes’ maximal respiration and spare respiratory capacity but increased their glycolytic capacity and glycolytic reserve. Further analysis found that 1-h treatment with different concentrations of glutamate （0.1-1 mmol/L） increased lactate release from astrocytes, however the cell viability was not affected by the glutamate treatment. Conclusion The current study provided direct evidence that exogenous glutamate treatment impaired the mitochondrial respiration capacity of astrocytes and enhanced aerobic glycolysis, which could be involved in glutamate injury or protection mechanisms in response to neurological disorders.展开更多
In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutama...In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutamate (Glu) were monitored simultaneously in vivo as indicators of rat’s excitatory state. Power spectral density (PSD) and gravity frequency of PSD were calculated. JuA (0.05 g/L and 0.1 g/L) inhibited the EEG excitation effect caused by Na-PCN by increasing the power of δ1 and δ2 bands (P<0.01 vs model) and lowering the gravity frequency of PSD (P<0.01 vs model). JuA also remarkably reduced the Glu elevation induced by Na-PCN (P<0.05 vs model). Diazepam also depressed Glu concentration and lowered the gravity frequency, but it showed a different EEG pattern in increased β2-activity (P<0.01 vs model). EEG excitation caused by Na-PCN correlated with Glu elevation during the first hour. Neurophysiological inhibitory effects of JuA and diazepam were more persistent than their Glu inhibitoty effects.展开更多
Recent studies show that a reduced effect of inhibitory transmitter system in the visual cortex may underlie aged visual function degradation. Whether excitatory transmitter system changes with age and hence affects i...Recent studies show that a reduced effect of inhibitory transmitter system in the visual cortex may underlie aged visual function degradation. Whether excitatory transmitter system changes with age and hence affects intracortical excitation-inhibition balance is not clear. To explore this issue, we used Nissl staining and immunohistochemical methods as well as Image-Pro Express software to examine the density of Nissl-stained neurons, Glutamie acid-immunoreactive （Glu-IR） neurons and T-Aminobutyric acid-immunoreactive （GABA-IR） neurons in the primary visual cortex of young adult and aged cats. The results showed that there was no significant difference in the density of Nissl-stained neurons between young and old cats （2〉0.05）. However, the density of Glu-IR neurons and GABA-IR neurons in the primary visual cortex of aged cats was significantly lower than that of young ones （P〈0.01）. The ratio between Glu-IR neurons and GABA-IR neurons was significantly increased in old cats compared to that in young adult ones （P〈0.01）. These results indicated that the effect of excitatory transmitter system in the old visual cortex was increased relative to the inhibitory transmitter system, which might cause an imbalance between cortical excitation and inhibition and might be an important factor mediating the visual function decline during aging.展开更多
As the global population ages,research on the pathogenesis and treatment options for older patients with dementia has become increasingly important.Vascular dementia(VaD),the second most frequent type of dementia,is c...As the global population ages,research on the pathogenesis and treatment options for older patients with dementia has become increasingly important.Vascular dementia(VaD),the second most frequent type of dementia,is characterized by vascular impairment caused by inadequate blood supply to the brain.VaD is a complex neurological disorder involving multiple cells and signaling pathways,and its prevention and treatment pose clinical challenges with significant behavioral implications.Glutamate,the most abundant amino acid in the brain,plays a critical role as an excitatory neurotransmitter,impacting cognitive function,learning,and memory.Abnormal glutamate metabolism has been closely linked to dementia,and reduced blood flow to the brain can lead to excessive glutamate accumulation,resulting in neuronal death.This article highlights the connection between VaD and glutamate metabolism,aiming to identify better methods for preventing and treating VaD via regulating glutamate metabolism.展开更多
基金supported by Georgia Research Alliance and the National Natural Science Foundation of China(Grant Nos.81320108025,61402194,61572227)the Science-Technology Development Project from Jilin Province(Nos.20160101259JC,20160204022GX,20170520063JH)
文摘Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.
基金supported by the National Natural Science Foundation of China,No.81471308,81271412the Natural Science Foundation of Liaoning Province of China,No.2014023052the Dalian Science and Technology Project Foundation of China,No.2015SF11GH094
文摘Rehmannia has been shown to be clinically effective in treating neurodegenerative diseases; however, the neuroprotective mechanisms remain unclear. In this study, we established a model of neurodegenerative disease using PC12 cytotoxic injury induced by glutamate. The cells were treated with 20 mM glutamate in the absence or presence of water extracts of dried Rehmannia root of varying concentrations（70%, 50% and 30%）. The different concentrations of Rehmannia water extract significantly increased the activity of glutamate-injured cells, reduced the release of lactate dehydrogenase, inhibited apoptosis, increased the concentrations of NADH, NAD and ATP in cells, ameliorated mitochondrial membrane potential, and reduced the levels of light chain 3. Taken together, our findings demonstrate that Rehmannia water extracts exert a cytoprotective effect against glutamate-induced PC12 cell injury via energy metabolism-related pathways.
基金supported by NIH/NCI ROICA140988-01 to JWpartially supported by Chinese Scholar Council to HY。
文摘Glutamine and glutamate are major bioenergy substrates for normal and cancer cell growth.Cancer cells need more biofuel than normal tissues for energy supply,anti-oxidation activity and biomass production.Genes related to metabolic chains in many cancers are somehow mutated,which makes cancer cells more glutamate dependent.Meanwhile,glutamate is an excitatory neurotransmitter for conducting signals through binding with different types of receptors in central neuron system.Interestingly,increasing evidences have shown involvement of glutamate signaling,guided through their receptors,in human malignancy.Dysregulation of glutamate transporters,such as excitatory amino acid transporter and cystine/glutamate antiporter system,also generates excessive extracellular glutamate,which in turn,activates glutamate receptors on cancer cells and results in malignant growth.These features make glutamate an attractive target for anti-cancer drug development with some glutamate targeted but blood brain barrier impermeable anti-psychosis drugs under consideration.We discussed the relevant progressions and drawbacks in this field herein.
基金supported by the National Natural Science Foundation of China,No.81271286Beijing Natural Science Foundation,No.7152027 to YUAN FangInnovation Foundation of Beijing Neurosurgical Institute,No.2014-11 to YAN Xu
文摘Objective To study the effect of glutamate on metabolism, shifts in glycolysis and lactate release in rat astrocytes. Methods After 10 days, secondary cultured astrocytes were treated with 1 mmol/L glutamate for 1 h, and the oxygen consumption rates （OCR） and extra cellular acidification rate （ECAR） was analyzed using a Seahorse XF 24 Extracellular Flux Analyzer. Cell viability was then evaluated by MTT assay. Moreover, changes in extracellular lactate concentration induced by glutamate were tested with a lactate detection kit. Results Compared with the control group, treatment with 1 mmol/L glutamate decreased the astrocytes’ maximal respiration and spare respiratory capacity but increased their glycolytic capacity and glycolytic reserve. Further analysis found that 1-h treatment with different concentrations of glutamate （0.1-1 mmol/L） increased lactate release from astrocytes, however the cell viability was not affected by the glutamate treatment. Conclusion The current study provided direct evidence that exogenous glutamate treatment impaired the mitochondrial respiration capacity of astrocytes and enhanced aerobic glycolysis, which could be involved in glutamate injury or protection mechanisms in response to neurological disorders.
基金Project supported by the National Natural Science Foundation ofChina (No. 30170275) and the Key Laboratory for Biomedical En-gineering of the Ministry of Education of China and Science andTechnology Department of Zhejiang Province (No. 011106239)
文摘In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutamate (Glu) were monitored simultaneously in vivo as indicators of rat’s excitatory state. Power spectral density (PSD) and gravity frequency of PSD were calculated. JuA (0.05 g/L and 0.1 g/L) inhibited the EEG excitation effect caused by Na-PCN by increasing the power of δ1 and δ2 bands (P<0.01 vs model) and lowering the gravity frequency of PSD (P<0.01 vs model). JuA also remarkably reduced the Glu elevation induced by Na-PCN (P<0.05 vs model). Diazepam also depressed Glu concentration and lowered the gravity frequency, but it showed a different EEG pattern in increased β2-activity (P<0.01 vs model). EEG excitation caused by Na-PCN correlated with Glu elevation during the first hour. Neurophysiological inhibitory effects of JuA and diazepam were more persistent than their Glu inhibitoty effects.
基金Natural Science Fund of Anhui Province (070413138)Key Laboratory Foundation of Anhui Province for Researches on the Conservation and Utilization of Important Biological ResourceKey Laboratory Foundation for Universities and Colleges in Anhui
文摘Recent studies show that a reduced effect of inhibitory transmitter system in the visual cortex may underlie aged visual function degradation. Whether excitatory transmitter system changes with age and hence affects intracortical excitation-inhibition balance is not clear. To explore this issue, we used Nissl staining and immunohistochemical methods as well as Image-Pro Express software to examine the density of Nissl-stained neurons, Glutamie acid-immunoreactive （Glu-IR） neurons and T-Aminobutyric acid-immunoreactive （GABA-IR） neurons in the primary visual cortex of young adult and aged cats. The results showed that there was no significant difference in the density of Nissl-stained neurons between young and old cats （2〉0.05）. However, the density of Glu-IR neurons and GABA-IR neurons in the primary visual cortex of aged cats was significantly lower than that of young ones （P〈0.01）. The ratio between Glu-IR neurons and GABA-IR neurons was significantly increased in old cats compared to that in young adult ones （P〈0.01）. These results indicated that the effect of excitatory transmitter system in the old visual cortex was increased relative to the inhibitory transmitter system, which might cause an imbalance between cortical excitation and inhibition and might be an important factor mediating the visual function decline during aging.
基金National Natural Science Foundation of China,Grant/AwardNumbers:82204376,82360710The Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi,Grant/AwardNumber:2022KY0505+2 种基金Fundof Guangxi ResearchandInnovationBasefor Basic and Clinical Application of Nerve Injury and RepairProject,Grant/AwardNumber:ZY21195042ResearchProject Fund forDrug Safety of Guangxi Food and Drug Administration,Grant/AwardNumber:GUIYA JINKESUZISHU[2023]No.008Guangxi Science and Technology Project,Grant/AwardNumber:AD171290015。
文摘As the global population ages,research on the pathogenesis and treatment options for older patients with dementia has become increasingly important.Vascular dementia(VaD),the second most frequent type of dementia,is characterized by vascular impairment caused by inadequate blood supply to the brain.VaD is a complex neurological disorder involving multiple cells and signaling pathways,and its prevention and treatment pose clinical challenges with significant behavioral implications.Glutamate,the most abundant amino acid in the brain,plays a critical role as an excitatory neurotransmitter,impacting cognitive function,learning,and memory.Abnormal glutamate metabolism has been closely linked to dementia,and reduced blood flow to the brain can lead to excessive glutamate accumulation,resulting in neuronal death.This article highlights the connection between VaD and glutamate metabolism,aiming to identify better methods for preventing and treating VaD via regulating glutamate metabolism.
