Lymphocytes respond to mitogens that stimulate proliferation by increasing theirs metabolic activity. In this study we investigate L-Glutamine and L-Leucine uptake as markers of cell response to Concavalina A (ConcaA)...Lymphocytes respond to mitogens that stimulate proliferation by increasing theirs metabolic activity. In this study we investigate L-Glutamine and L-Leucine uptake as markers of cell response to Concavalina A (ConcaA) stimulation, using a high-resolution flow technique. We found that lymphocytes induced to blast transformation enhanced rate and efficiency of amino acid uptake during cell proliferation. Considering that increases in transport is the first quantifiable response of cells during malignant transformation, amino acid uptake could also be useful as an early marker of malignancy.展开更多
Negative direct current (__DC 300 μA) stimulation was applied to the round window ofthe guinea pig cochlea to exhaust the pre-synaptic intracellular reserves of the transmitter inhair cells, and then the scala tympan...Negative direct current (__DC 300 μA) stimulation was applied to the round window ofthe guinea pig cochlea to exhaust the pre-synaptic intracellular reserves of the transmitter inhair cells, and then the scala tympani was perfused respectively with L- glutamine, glutaminesynthetase and glutaminase. Experimental results showed that the negative DC electricalstimulation applied to the round window elevated the CAP threshold of the cochlear nervein the basal turn of the cochlea, which recovered over a period of approximately 17- 39 min.The perfusion of L- glutamine apparently elevated the CAP threshold. The recovery of theCAP threshold following electrical stimulation, however, was accelerated by the perfusion of10 mmol/L L- glutamine. The time for recovery only took about 5- 6 min. The perfusion ofenzyme glutamine synthetase elevated the CAP threshold by 50 dB, while glutaminase hadlittle effect. These results suggest that the effect of L- glutamine on the CAP threshold inthe cocblea of the guinea pig appears to be that of a potent depolarizing agent which acceler-ates the recovery of the CAP threshold during the depletion of the transmitter, and L-glutamine may be the candidate for the afferent excitatory transmitter.展开更多
Different amino acids have been shown to affect feed intake when injected directly into the central nervous system of birds. In the present study, we investigated the effects of L-glutamine and L-alanine on feed intak...Different amino acids have been shown to affect feed intake when injected directly into the central nervous system of birds. In the present study, we investigated the effects of L-glutamine and L-alanine on feed intake and the mRNA expression levels of hypothalamic neuropeptides involved in feed intake regulation in broiler chicks. L-Glutamine or L- alanine was intra-cerebroventricularly （ICV） administered to 4-d-old broiler chicks and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of neuropeptide Y （NPY）, agouti related protein （AgRP）, pro-opiomelanocortin （POMC）, melanocortin receptor 4 （MC4R） and corticotropin releasing factor （CRF）. Our results showed that ICV administration of L-glutamine （0.55 or 5.5 pmol） significantly increased feed intake up to 2 h post-administration period and the hypothalamic NPY mRNA expression levels, while it markedly decreased hypothalamic POMC and CRF mRNA expression levels. In contrast, ICV administration of L-alanine （4 lamol） significantly decreased feed intake for the first 0.5 h post-administration period, and reduced the hypothalamic AgRP mRNA expression levels, while it remarkablely enhanced the mRNA expression levels of MC4R and CRF. These findings suggested that L-glutamine and L-alanine could act within the hypothalamus to influence feed intake in broiler chicks, and that both orexigenic and anorexigenic neuropeptide genes might contribute directly to these effects.展开更多
The effects of the supplementation with L-glutamine(GLN)or L-alanyl-L-glutamine(GDP)on the progression of the systemic and hepatic metabolic status of rats having untreated type 1 diabetes mellitus(T1DM)were investiga...The effects of the supplementation with L-glutamine(GLN)or L-alanyl-L-glutamine(GDP)on the progression of the systemic and hepatic metabolic status of rats having untreated type 1 diabetes mellitus(T1DM)were investigated.Male Wistar diabetic rats(streptozotocin,60 mg/kg)were allotted to four groups supplemented by gavage for thirty days as follows:control and diabetic receiving saline;diabetic receiving GLN(248 mg/kg);and diabetic receiving GDP(400 mg/kg).Body weight,plasmatic parameters and kidney function were analyzed.Isolated hepatocytes were used to assess gluconeogenic capacity.Liver and kidney were used for morphological analyses.T1DM decreased the number and increased the area of the hepatocytes,possibly because of the observed enlargement of glycogen stores.Kidney weight,glomerular area and proteinuria increased,and glomerular filtration rate decreased,in non-supplemented T1DM rats.Glomerular area and proteinuria were reversed by both supplementations.The T1DM hepatocytes released less glucose,which could have been diverted to glycogen synthesis and secondary glycogenosis observed in T1DM;this was partially reversed by the supplementations.The results point to a possible beneficial effect of glutamine on the metabolic and hepatic impairments of T1DM.展开更多
Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary glioblastomas.Mutant IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by red...Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary glioblastomas.Mutant IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by reducing α-ketoglutarate(α-KG),a central player in metabolism and epigenetic modifications.However,the role ofα-KG homeostasis in IDH-mutated gliomagenesis remains elusive.In this study,we found that low expression of oxoglutarate dehydrogenase(OGDH)was a common feature in IDH-mutated gliomas,as well as inastrocytes.This low expression of OGDH resultedin the accumulation of α-KG and promoted astrocyte maturation.However,IDH1 mutation significantly reducedα-KG levels and increased glutaminolysis and DNA/histone methylation in astrocytes.These metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in mice.Moreover,our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells,while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation ofα-KG and increasing glutaminolysis.Finally,we found that l-glutamine increasedα-KG levels and augmented the differentiation-promoting effects of AGI5198,an IDH1-mutant inhibitor,in IDH1-mutant glioma cells.Collectively,this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas,providing a potential strategy for the treatment of IDH-mutant gliomas by targetingα-KG homeostasis.展开更多
文摘Lymphocytes respond to mitogens that stimulate proliferation by increasing theirs metabolic activity. In this study we investigate L-Glutamine and L-Leucine uptake as markers of cell response to Concavalina A (ConcaA) stimulation, using a high-resolution flow technique. We found that lymphocytes induced to blast transformation enhanced rate and efficiency of amino acid uptake during cell proliferation. Considering that increases in transport is the first quantifiable response of cells during malignant transformation, amino acid uptake could also be useful as an early marker of malignancy.
文摘Negative direct current (__DC 300 μA) stimulation was applied to the round window ofthe guinea pig cochlea to exhaust the pre-synaptic intracellular reserves of the transmitter inhair cells, and then the scala tympani was perfused respectively with L- glutamine, glutaminesynthetase and glutaminase. Experimental results showed that the negative DC electricalstimulation applied to the round window elevated the CAP threshold of the cochlear nervein the basal turn of the cochlea, which recovered over a period of approximately 17- 39 min.The perfusion of L- glutamine apparently elevated the CAP threshold. The recovery of theCAP threshold following electrical stimulation, however, was accelerated by the perfusion of10 mmol/L L- glutamine. The time for recovery only took about 5- 6 min. The perfusion ofenzyme glutamine synthetase elevated the CAP threshold by 50 dB, while glutaminase hadlittle effect. These results suggest that the effect of L- glutamine on the CAP threshold inthe cocblea of the guinea pig appears to be that of a potent depolarizing agent which acceler-ates the recovery of the CAP threshold during the depletion of the transmitter, and L-glutamine may be the candidate for the afferent excitatory transmitter.
基金the National Basic Research Program of China (2009CB941601)the Joint Funds of the National Natural Science Foundation of China (u0731004)+3 种基金the National Natural Science Foundation of China(30871845, 30901058 and 30972157)the Natural Science Foundation of Guangdong Province of China(9451064201003790 and 9151064201000056)the National Public Benefit (Agricultural) Research Foundation of China(201003011)the Specialized Research Fund for the Doctoral Program of Higher Education of China(20094404120012)
文摘Different amino acids have been shown to affect feed intake when injected directly into the central nervous system of birds. In the present study, we investigated the effects of L-glutamine and L-alanine on feed intake and the mRNA expression levels of hypothalamic neuropeptides involved in feed intake regulation in broiler chicks. L-Glutamine or L- alanine was intra-cerebroventricularly （ICV） administered to 4-d-old broiler chicks and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of neuropeptide Y （NPY）, agouti related protein （AgRP）, pro-opiomelanocortin （POMC）, melanocortin receptor 4 （MC4R） and corticotropin releasing factor （CRF）. Our results showed that ICV administration of L-glutamine （0.55 or 5.5 pmol） significantly increased feed intake up to 2 h post-administration period and the hypothalamic NPY mRNA expression levels, while it markedly decreased hypothalamic POMC and CRF mRNA expression levels. In contrast, ICV administration of L-alanine （4 lamol） significantly decreased feed intake for the first 0.5 h post-administration period, and reduced the hypothalamic AgRP mRNA expression levels, while it remarkablely enhanced the mRNA expression levels of MC4R and CRF. These findings suggested that L-glutamine and L-alanine could act within the hypothalamus to influence feed intake in broiler chicks, and that both orexigenic and anorexigenic neuropeptide genes might contribute directly to these effects.
文摘The effects of the supplementation with L-glutamine(GLN)or L-alanyl-L-glutamine(GDP)on the progression of the systemic and hepatic metabolic status of rats having untreated type 1 diabetes mellitus(T1DM)were investigated.Male Wistar diabetic rats(streptozotocin,60 mg/kg)were allotted to four groups supplemented by gavage for thirty days as follows:control and diabetic receiving saline;diabetic receiving GLN(248 mg/kg);and diabetic receiving GDP(400 mg/kg).Body weight,plasmatic parameters and kidney function were analyzed.Isolated hepatocytes were used to assess gluconeogenic capacity.Liver and kidney were used for morphological analyses.T1DM decreased the number and increased the area of the hepatocytes,possibly because of the observed enlargement of glycogen stores.Kidney weight,glomerular area and proteinuria increased,and glomerular filtration rate decreased,in non-supplemented T1DM rats.Glomerular area and proteinuria were reversed by both supplementations.The T1DM hepatocytes released less glucose,which could have been diverted to glycogen synthesis and secondary glycogenosis observed in T1DM;this was partially reversed by the supplementations.The results point to a possible beneficial effect of glutamine on the metabolic and hepatic impairments of T1DM.
基金supported by funds from the National Key Research and Development Program of China(2022YFA0806501)the National Natural Science Foundation of China(81972342 to J.Y.,82173120 to Y.G.,and 82070298 to L.Z.)the Natural Science Basic Research Plan in ShaanxiProvince(2020JZ-29 to J.Y.).
文摘Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary glioblastomas.Mutant IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by reducing α-ketoglutarate(α-KG),a central player in metabolism and epigenetic modifications.However,the role ofα-KG homeostasis in IDH-mutated gliomagenesis remains elusive.In this study,we found that low expression of oxoglutarate dehydrogenase(OGDH)was a common feature in IDH-mutated gliomas,as well as inastrocytes.This low expression of OGDH resultedin the accumulation of α-KG and promoted astrocyte maturation.However,IDH1 mutation significantly reducedα-KG levels and increased glutaminolysis and DNA/histone methylation in astrocytes.These metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in mice.Moreover,our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells,while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation ofα-KG and increasing glutaminolysis.Finally,we found that l-glutamine increasedα-KG levels and augmented the differentiation-promoting effects of AGI5198,an IDH1-mutant inhibitor,in IDH1-mutant glioma cells.Collectively,this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas,providing a potential strategy for the treatment of IDH-mutant gliomas by targetingα-KG homeostasis.
