Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptak...Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptake systems, which utilize the electrochemical proton gradient as a driving force. Three vesicular glutamate transporters (VGLUT1-3) have been recently identified from neuronal tissue where they play a key role to maintain the vesicular glutamate level. Recently, it has been demonstrated that glutamate signaling is also functional in peripheral neuronal and non-neuronal tissues, and occurs in sites of pituitary, adrenal, pineal glands, bone, GI tract, pancreas,skin, and testis. The glutamate receptors and VGLUTs in digestivesystem have been found in both neuronal and endocrinal cells. The glutamate signaling in the digestive system may have significant relevance to diabetes and GI tract motility disorders. This review will focus on the most recent update of molecular physiology of digestive VGLUTs.展开更多
The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rat...The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin,it was found that these cell types respond differentially to the duration and concentration of erastin treatment.Therefore,we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos.After treatment with 50μM erastin for 48 hours,reactive oxygen species levels increased,and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased.Pretreatment with deferoxamine for 12 hours inhibited these changes,reduced cell death,and ameliorated cellular morphology.Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis.Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin,confirming the specificity of the in vitro ferroptosis model.This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences,China(approval No.DWLL-20180913)on September 13,2018.展开更多
In the peripheral nervous system,the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves.Axons within the nerves are in close contact with myelinating glia,the Schwan...In the peripheral nervous system,the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves.Axons within the nerves are in close contact with myelinating glia,the Schwann cells that are ideally placed to respond to,and possibly shape,axonal activity.The mechanisms of intercellular communication in the peripheral nerves may involve direct contact between the cells,as well as signalling via diffusible substances.Neurotransmitter glutamate has been proposed as a candidate extracellular molecule mediating the cross-talk between cells in the peripheral nerves.Two types of experimental findings support this idea:first,glutamate has been detected in the nerves and can be released upon electrical or chemical stimulation of the nerves;second,axons and Schwann cells in the peripheral nerves express glutamate receptors.Yet,the studies providing direct experimental evidence that intercellular glutamatergic signalling takes place in the peripheral nerves during physiological or pathological conditions are largely missing.Remarkably,in the central nervous system,axons and myelinating glia are involved in glutamatergic signalling.This signalling occurs via different mechanisms,the most intriguing of which is fast synaptic communication between axons and oligodendrocyte precursor cells.Glutamate receptors and/or synaptic axon-glia signalling are involved in regulation of proliferation,migration,and differentiation of oligodendrocyte precursor cells,survival of oligodendrocytes,and re-myelination of axons after damage.Does synaptic signalling exist between axons and Schwann cells in the peripheral nerves?What is the functional role of glutamate receptors in the peripheral nerves?Is activation of glutamate receptors in the nerves beneficial or harmful during diseases?In this review,we summarise the limited information regarding glutamate release and glutamate receptors in the peripheral nerves and speculate about possible mechanisms of glutamatergic signalling in the nerves.We highli展开更多
基金Supported by the National Institute of Diabetes and Digestive Kidney Diseases Grant R01-DK063142 and R01-DK33209
文摘Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptake systems, which utilize the electrochemical proton gradient as a driving force. Three vesicular glutamate transporters (VGLUT1-3) have been recently identified from neuronal tissue where they play a key role to maintain the vesicular glutamate level. Recently, it has been demonstrated that glutamate signaling is also functional in peripheral neuronal and non-neuronal tissues, and occurs in sites of pituitary, adrenal, pineal glands, bone, GI tract, pancreas,skin, and testis. The glutamate receptors and VGLUTs in digestivesystem have been found in both neuronal and endocrinal cells. The glutamate signaling in the digestive system may have significant relevance to diabetes and GI tract motility disorders. This review will focus on the most recent update of molecular physiology of digestive VGLUTs.
基金supported by the National Natural Science Foundation of China,Nos.81672171(to XY),81620108018(to SQF),81772342(to GZN)the State Key Laboratory of Medicinal Chemical Biology of Nankai University of China,No.2017027(to XY)
文摘The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin,it was found that these cell types respond differentially to the duration and concentration of erastin treatment.Therefore,we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos.After treatment with 50μM erastin for 48 hours,reactive oxygen species levels increased,and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased.Pretreatment with deferoxamine for 12 hours inhibited these changes,reduced cell death,and ameliorated cellular morphology.Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis.Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin,confirming the specificity of the in vitro ferroptosis model.This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences,China(approval No.DWLL-20180913)on September 13,2018.
基金the laboratory of Maria Kukley was supported by the Excellence Strategy Program of the University of Tübingen(Deutsche Forschungsgemeinschaft,ZUK63)
文摘In the peripheral nervous system,the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves.Axons within the nerves are in close contact with myelinating glia,the Schwann cells that are ideally placed to respond to,and possibly shape,axonal activity.The mechanisms of intercellular communication in the peripheral nerves may involve direct contact between the cells,as well as signalling via diffusible substances.Neurotransmitter glutamate has been proposed as a candidate extracellular molecule mediating the cross-talk between cells in the peripheral nerves.Two types of experimental findings support this idea:first,glutamate has been detected in the nerves and can be released upon electrical or chemical stimulation of the nerves;second,axons and Schwann cells in the peripheral nerves express glutamate receptors.Yet,the studies providing direct experimental evidence that intercellular glutamatergic signalling takes place in the peripheral nerves during physiological or pathological conditions are largely missing.Remarkably,in the central nervous system,axons and myelinating glia are involved in glutamatergic signalling.This signalling occurs via different mechanisms,the most intriguing of which is fast synaptic communication between axons and oligodendrocyte precursor cells.Glutamate receptors and/or synaptic axon-glia signalling are involved in regulation of proliferation,migration,and differentiation of oligodendrocyte precursor cells,survival of oligodendrocytes,and re-myelination of axons after damage.Does synaptic signalling exist between axons and Schwann cells in the peripheral nerves?What is the functional role of glutamate receptors in the peripheral nerves?Is activation of glutamate receptors in the nerves beneficial or harmful during diseases?In this review,we summarise the limited information regarding glutamate release and glutamate receptors in the peripheral nerves and speculate about possible mechanisms of glutamatergic signalling in the nerves.We highli
