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Researching glutamate - induced cytotoxicity in different cell lines: a comparative/collective analysis/study.

Kritis AA, Stamoula EG, Paniskaki KA, Vavilis TD - Front Cell Neurosci (2015)

Bottom Line: Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione's reducing potential.However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative.Different cell lines differ in their responses when exposed to glutamate.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Physiology, Department of Physiology and Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki Greece.

ABSTRACT
Although glutamate is one of the most important excitatory neurotransmitters of the central nervous system, its excessive extracellular concentration leads to uncontrolled continuous depolarization of neurons, a toxic process called, excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular Ca(2+) levels, followed by up regulation of nNOS, dysfunction of mitochondria, ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium concentration is the key mediator of glutamate toxicity through over activation of ionotropic and metabotropic receptors. In addition, glutamate accumulation can also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate antiporter. Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione's reducing potential. Various cell lines have been employed in the pursuit to understand the mechanism(s) by which excitotoxicity affects the cells leading them ultimately to their demise. In some cell lines glutamate toxicity is exerted mainly through over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines lacking such receptors, the toxicity is due to glutamate induced oxidative stress. However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative. Different cell lines differ in their responses when exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT-22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems are systematically collected and analyzed.

No MeSH data available.


Related in: MedlinePlus

Glutamate receptors: structure and function. NMDARs bind glutamate, glycine, Mg2+, Zn2+, and polyamines. Composed from seven subunits (one NR1, four NR2, and two NR3), their function is determined by the combination of NR1 and NR2 subunits. NMDARs form channels that are more permeable to Ca2+ than Na+ and K+. Kainate and AMPA receptors interact only with glutamate and their specific agonists, and their associated channels are more permeable to Na+ and K+ than Ca2+. mGluRs are G-protein coupled receptors and trigger a second messenger cascade. They are found both at the pre- and post-synaptic neurons, subunits of metabotropic receptors are also expressed in microglia.
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Figure 2: Glutamate receptors: structure and function. NMDARs bind glutamate, glycine, Mg2+, Zn2+, and polyamines. Composed from seven subunits (one NR1, four NR2, and two NR3), their function is determined by the combination of NR1 and NR2 subunits. NMDARs form channels that are more permeable to Ca2+ than Na+ and K+. Kainate and AMPA receptors interact only with glutamate and their specific agonists, and their associated channels are more permeable to Na+ and K+ than Ca2+. mGluRs are G-protein coupled receptors and trigger a second messenger cascade. They are found both at the pre- and post-synaptic neurons, subunits of metabotropic receptors are also expressed in microglia.

Mentions: N-methyl-D-aspartate receptors are complex structures able to bind glutamate, glycine, Mg2+, Zn2+, and polyamines. Composed from seven subunits (one NR1, four NR2, and two NR3), their function is determined by the combination of NR1 and NR2 subunits. NMDARs form channels that are more permeable to Ca2+ than Na+ and K+. Upon binding of glutamate the magnesium ions, blocking the ion channel, are released and consequently the ion channel is activated allowing the influx of the aforementioned ions into the cytoplasm (Mehta et al., 2012). Kainate and AMPA receptors interact only with glutamate and their specific agonists, and their associated channels are more permeable to Na+ and K+ than Ca2+(Kostandy, 2012; Figure 2).


Researching glutamate - induced cytotoxicity in different cell lines: a comparative/collective analysis/study.

Kritis AA, Stamoula EG, Paniskaki KA, Vavilis TD - Front Cell Neurosci (2015)

Glutamate receptors: structure and function. NMDARs bind glutamate, glycine, Mg2+, Zn2+, and polyamines. Composed from seven subunits (one NR1, four NR2, and two NR3), their function is determined by the combination of NR1 and NR2 subunits. NMDARs form channels that are more permeable to Ca2+ than Na+ and K+. Kainate and AMPA receptors interact only with glutamate and their specific agonists, and their associated channels are more permeable to Na+ and K+ than Ca2+. mGluRs are G-protein coupled receptors and trigger a second messenger cascade. They are found both at the pre- and post-synaptic neurons, subunits of metabotropic receptors are also expressed in microglia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362409&req=5

Figure 2: Glutamate receptors: structure and function. NMDARs bind glutamate, glycine, Mg2+, Zn2+, and polyamines. Composed from seven subunits (one NR1, four NR2, and two NR3), their function is determined by the combination of NR1 and NR2 subunits. NMDARs form channels that are more permeable to Ca2+ than Na+ and K+. Kainate and AMPA receptors interact only with glutamate and their specific agonists, and their associated channels are more permeable to Na+ and K+ than Ca2+. mGluRs are G-protein coupled receptors and trigger a second messenger cascade. They are found both at the pre- and post-synaptic neurons, subunits of metabotropic receptors are also expressed in microglia.
Mentions: N-methyl-D-aspartate receptors are complex structures able to bind glutamate, glycine, Mg2+, Zn2+, and polyamines. Composed from seven subunits (one NR1, four NR2, and two NR3), their function is determined by the combination of NR1 and NR2 subunits. NMDARs form channels that are more permeable to Ca2+ than Na+ and K+. Upon binding of glutamate the magnesium ions, blocking the ion channel, are released and consequently the ion channel is activated allowing the influx of the aforementioned ions into the cytoplasm (Mehta et al., 2012). Kainate and AMPA receptors interact only with glutamate and their specific agonists, and their associated channels are more permeable to Na+ and K+ than Ca2+(Kostandy, 2012; Figure 2).

Bottom Line: Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione's reducing potential.However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative.Different cell lines differ in their responses when exposed to glutamate.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Physiology, Department of Physiology and Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki Greece.

ABSTRACT
Although glutamate is one of the most important excitatory neurotransmitters of the central nervous system, its excessive extracellular concentration leads to uncontrolled continuous depolarization of neurons, a toxic process called, excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular Ca(2+) levels, followed by up regulation of nNOS, dysfunction of mitochondria, ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium concentration is the key mediator of glutamate toxicity through over activation of ionotropic and metabotropic receptors. In addition, glutamate accumulation can also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate antiporter. Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione's reducing potential. Various cell lines have been employed in the pursuit to understand the mechanism(s) by which excitotoxicity affects the cells leading them ultimately to their demise. In some cell lines glutamate toxicity is exerted mainly through over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines lacking such receptors, the toxicity is due to glutamate induced oxidative stress. However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative. Different cell lines differ in their responses when exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT-22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems are systematically collected and analyzed.

No MeSH data available.


Related in: MedlinePlus