Consolidation of transient ionotropic glutamate signals through nuclear transcription factors in the brain

Yoneda, Yukio; Kuramoto, Nobuyuki; Kitayama, Tomoya; Hinoi, Eiichi

doi:10.1016/s0301-0082(00)00036-8

Cited by 59 publications

(35 citation statements)

References 124 publications

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“…Both AMPA 254 and NMDA receptors 255 are probably largely formed from tetrameric, heteromeric assemblies of different subunits 256 . Changes in these receptors are probably mediated through nuclear transcription factors 257 .…”

Section: The Iglur Family Is Classified Into Three Major Subtypes a Cmentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

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Section: The Iglur Family Is Classified Into Three Major Subtypes a Cmentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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“…The pellets were suspended in DMEM containing 10% FBS. Cells were plated at a density of 4ϫ10 4 /cm 2 in 24-well dishes, followed by culturing at 37°C under 5% CO 2 for additional 6 d. Culture medium was exchanged to DMEM supplemented with 10% FBS and 50 mg/ml ascorbic acid for subsequent culturing for different periods up to 28 d. Medium was changed every 2 to 3 d.…”

Section: MD Usa)mentioning

confidence: 99%

Release of Endogenous Glutamate by AMPA Receptors Expressed in Cultured Rat Costal Chondrocytes

Wang

Hinoi

Takemori

et al. 2005

Biological & Pharmaceutical Bulletin

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L-Glutamate (Glu) is one of the most abundant free amino acids with a major excitatory neurotransmitter role in the vertebrate central nervous system, while recent trends are toward a role in neuronal differentiation, migration and survival in the developing brain.2-4) The actions of extracellular Glu are mediated by membranous receptors, which can be divided into two major groups. 4) One is ionotropic Glu-gated ion channels (iGluRs) that are further classified into DL-aamino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA), kainite (KA) and N-methyl-D-aspartate (NMDA) subtypes according to sequential similarities as well as responsiveness to different agonists and antagonists, 5,6) whereas the other is G-protein-coupled metabotropic receptors (mGluRs) that are a member of the class 3 G protein-coupled receptor family. 7,8) In addition to GluRs, vesicular Glu transporters (VGLUTs) are essential for signal output through the condensation of Glu into vesicular constituents for subsequent exocytotic release. Within the central nervous system (CNS), both VGLUT-1 9) and VGLUT-2 10) isoforms are supposed to suffice for the definition of an excitatory neuronal phenotype, while VGLUT3 is expressed in a number of cells shown to release Glu through exocytosis including dopaminergic, GABAergic and serotonergic neurons as well as astrocytes. 11)Recently, evidence that glutamatergic signaling is also functional in non-neuronal tissues, such as bone, pancreas and skin, is accumulating in the literature.12,13) Glu may act as a more widespread "cytokine" rather than a "neurotransmitter" to influence a variety of cellular activities in different tissue types. 12,13) Recent studies have raised the possibility that Glu may be one of the endogenous paracrine (autocrine) factors used for intercellular communications in bone. 14,15) The addition of an NMDA receptor antagonist inhibits cell differentiation in cultured osteoclasts, 16) for example, while Glu induces elevation of intracellular free Ca 2ϩ in a manner sensitive to antagonism by the NMDA receptor antagonist dizocilpine in osteoblasts. 17) We have also recently demonstrated the exacerbation of osteoblastic differentiation by different NMDA receptor antagonists.18) In addition to NMDA receptors, osteoblasts constitutively express mRNA for non-NMDA receptors such as GluR3 subunit of AMPA receptors (AMPAR) as well as KA1 and KA2 subunits of KA receptors, 19) while AMPAR modulate the exocytotic release of Glu from cultured osteoblasts. 20) By contrast, no much attention has been paid to the possible functional expression by cartilage of particular glutamatergic signaling molecules required for the neurotransmission in the brain to date. Therefore, we have attempted to mimic our previous studies on cultured rat osteoblasts for the release of endogenous Glu using cultured rat chondrocytes. In the present study, functional expression was for the first time shown with a particular subtype of iGluRs in cartilage. MATERIALS AND METHODSMaterials Leica CM 3050s cryostat and a fluorescen...

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“…Extracellular levels of glutamate are determined by the glutamate transporter [1,2] . The diverse actions of L-glutamate in the CNS result from the existence of multiple glutamate receptors (GluR).…”

Section: Introductionmentioning

confidence: 99%

Multiple signaling pathways involved in stimulation of osteoblast differentiation by N-methyl-D-aspartate receptors activation in vitro

Zhao

Cui

et al. 2011

Acta Pharmacol Sin

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Aim: Glutamate receptors are expressed in osteoblastic cells. The present study was undertaken to investigate the mechanisms underlying the stimulation of osteoblast differentiation by N-methyl-D-aspartate (NMDA) receptor activation in vitro. Methods: Primary culture of osteoblasts was prepared from SD rats. Microarray was used to detect the changes of gene expression. The effect of NMDA receptor agonist or antagonist on individual gene was examined using RT-PCR. The activity of alkaloid phosphotase (ALP) was assessed using a commercial ALP staining kit. Results: Microarray analyses revealed that 10 genes were up-regulated by NMDA (0.5 mmol/L) and down-regulated by MK801 (100 μmol/L), while 13 genes down-regulated by NMDA (0.5 mmol/L) and up-regulated by MK801 (100 μmol/L). Pretreatment of osteoblasts with the specific PKC inhibitor Calphostin C (0.05 μmol/L), the PKA inhibitor H-89 (20 nmol/L), or the PI3K inhibitor wortmannin (100 nmol/L) blocked the ALP activity increase caused by NMDA (0.5 mmol/L). Furthermore, NMDA (0.5 mmol/L) rapidly increased PI3K phosphorylation, which could be blocked by pretreatment of wortmannin (100 nmol/L). Conclusion:The results suggest that activation of NMDA receptors stimulates osteoblasts differentiation through PKA, PKC, and PI3K signaling pathways, which is a new role for glutamate in regulating bone remodeling.

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Consolidation of transient ionotropic glutamate signals through nuclear transcription factors in the brain

Cited by 59 publications

References 124 publications

A Review of Glutamate Receptors I: Current Understanding of Their Biology

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Release of Endogenous Glutamate by AMPA Receptors Expressed in Cultured Rat Costal Chondrocytes

Multiple signaling pathways involved in stimulation of osteoblast differentiation by N-methyl-D-aspartate receptors activation in vitro

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