Glutamine Synthetase and Glutamine Synthetase‐Like Protein from Human Brain

Boksha, Irina S.; Tereshkina, Elena B.; Бурбаева, Г. Ш.

doi:10.1046/j.1471-4159.2000.0752574.x

Cited by 29 publications

(26 citation statements)

References 31 publications

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“…These data complement our previous results on altered level of GME and CK BB in cytoplasm fraction of PFC tissue [23,29]. Since the new extraction method used in present study takes into account particulate isoforms, such as GDH III and partially GSLP [41,42] in addition to cytoplasm isoforms, we are confident that we have measured total amounts of target proteins in the brain tissue. Unlike our previous experiments with cytoplasm fraction of PFC [23,29,37], in the current study we did not observe any difference in the level of total CK BB, GSLP, or GDH III between control and SCH groups in this brain region (and in CN or cerebellum as well).…”

Section: Discussionsupporting

confidence: 90%

“…4673-5007, Clone No. 49G3, Biogenesis, UK) at 1:1,000,000 working dilution; the amount of GSLP immunoreactive protein and the levels of GDH isoforms (readily soluble GDH I + II and associated with particulate fraction GDH III) were evaluated in brain extracts using specific rabbit antisera raised in the Laboratory of Neurochemistry MHRC RAMS and described earlier [41,42], each at 1:10,000 working dilution;…”

Section: Internal Standardmentioning

confidence: 99%

“…For these proteins a sum of both bands' intensities was calculated for each sample. GSLP was represented by 54 kDa-band (corresponding to a subunit of previously described cytoplasm form [41]) and 50 kDa-band (presenting in extracts prepared by boiling with SDS, as described above). GDH I + II was presented by 56 and 58-kDa protein bands, corresponding to cytoplasm forms [42].…”

Section: Internal Standardmentioning

confidence: 99%

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Systemic Neurochemical Alterations in Schizophrenic Brain: Glutamate Metabolism in Focus

et al. 2007

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We have used a systemic approach to establish a relationship between enzyme measures of glial glutamate and energy metabolism (glutamine synthetase and glutamine synthetase-like protein, glutamate dehydrogenase isoenzymes, brain isoform creatine phosphokinase) and two major glial proteins (glial fibrillary acidic protein and myelin basic protein) in autopsied brain samples taken from patients with schizophrenia (SCH) and mentally healthy subjects (23 and 22 cases, respectively). These biochemical parameters were measured in tissue extracts in three brain areas (prefrontal cortex, caudate nucleus, and cerebellum). Significant differences in the level of at least one of the glutamate metabolizing enzymes were observed between two studied groups in all studied brain areas. Different patterns of correlative links between the biochemical parameters were found in healthy and schizophrenic brains. These findings give a new perspective to our understanding of the impaired regulation of enzyme levels in the brain in SCH.

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Section: Discussionsupporting

confidence: 90%

Section: Internal Standardmentioning

confidence: 99%

Section: Internal Standardmentioning

confidence: 99%

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Systemic Neurochemical Alterations in Schizophrenic Brain: Glutamate Metabolism in Focus

et al. 2007

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“…A proteomic study by Prabakaran et al also described reduced glutamine synthetase in schizophrenia in area 9 of the frontal cortex (Prabakaran et al, 2004). Consistent with reports of multiple isoforms of glutamine synthetase (Chakrabarti et al, 1995;Boksha et al, 2000), the study by Burbaeva et al also showed that protein expression of an enzyme similar in activity and immunoreactivity to glutamine synthetase, termed glutamine synthetase like protein (GSLP), was increased in this brain region. In addition to protein levels, this study measured the transferase activity of glutamine synthetase and GSLP; however, no changes were detected.…”

Section: Expression Of Glutamine Synthetase In Schizophreniamentioning

confidence: 57%

Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia

Steffek¹,

McCullumsmith²,

Haroutunian³

et al. 2008

Schizophrenia Research

110

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Altered expression of structural and functional molecules expressed by astrocytes may play a role in the pathophysiology of schizophrenia. We investigated the hypothesis that the astrocytic enzyme glutamine synthetase, involved in maintaining the glutamate-glutamine cycle, and the cytoskeletal molecule glial fibrillary acidic protein (GFAP) are abnormally expressed in schizophrenia. We used Western blot analysis to measure levels of glutamine synthetase and GFAP in several brain regions of subjects with schizophrenia and a comparison group. We found that glutamine synthetase protein expression was significantly decreased in the superior temporal gyrus, and both glutamine synthetase and GFAP were significantly reduced in the anterior cingulate cortex in schizophrenia. Neither molecule demonstrated altered expression in the dorsolateral prefrontal cortex, primary visual cortex, or hippocampus. Chronic treatment with haloperidol did not alter the expression of these molecules in the rat brain, suggesting that our findings are not due to a medication effect. These data support an astrocytic component to the pathophysiology of schizophrenia and suggest that astrocytic molecules involved in enzymatic activity and cytoskeletal integrity may have a role in disease-related abnormalities in this illness.

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“…Brain glutamine synthase enzymatic activity was routinely measured as previously described (Boksha et al, 2000) by the transferase reaction (ADP+L-Gln+NH2OH) and was determined by measuring -glutamyl hydroxamate formation. Cells were treated with cyclic adenosine monophosphate (Sigma Aldrich, 100 mM, 3 h) and subsequently with glutamate (Sigma Aldrich, 1 mM, 1 h).…”

Section: Glutamine Synthetase Activitymentioning

confidence: 99%

Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury

Marignier

Nicolle

Watrin

et al. 2010

Brain

162

138

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Devic's neuromyelitis optica is an inflammatory demyelinating disorder normally restricted to the optic nerves and spinal cord. Since the identification of a specific autoantibody directed against aquaporin 4, neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody, neuromyelitis optica has been considered an entity distinct from multiple sclerosis. Recent findings indicate that the neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody has a pathogenic role through complementdependent astrocyte toxicity. However, the link with demyelination remains elusive. Autoantibodies can act as receptor agonists/antagonists or alter antigen density in their target cells. We hypothesized that the neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody impairs astrocytic function and secondarily leads to demyelination. Rat astrocytes and oligodendrocytes from primary cultures and rat optic nerves were exposed long-term (24 h) to immunoglobulin G in the absence of complement. Immunoglobulin G was purified from the serum of patients with neuromyelitis optica who were either neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody positive or negative, as well as from healthy controls. Flow cytometry analysis showed a reduction of membrane aquaporin 4 and glutamate transporter type 1 on astrocytes following contact with immunoglobulin G purified from neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody positive serum only. The activity of glutamine synthetase, an astrocyte enzyme converting glutamate into glutamine, decreased in parallel, indicating astrocyte dysfunction. Treatment also reduced oligodendrocytic cell processes and approximately 30% oligodendrocytes died. This deleterious effect was confirmed ex vivo; exposed optic nerves showed reduction of myelin basic protein. Immunoglobulin G from neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody seronegative patients and from healthy controls had no similar effect. Neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody did not directly injure oligodendrocytes cultured without astrocytes. A toxic bystander effect of astrocytes damaged by neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody on oligodendrocytes was identified. Progressive accumulation of glutamate in the culture medium of neuromyelitis opticaimmunoglobulin G/aquaporin 4-antibody-treated glial cells supported the hypothesis of a glutamate-mediated excitotoxic death of oligodendrocytes in our models. Moreover, co-treatment of glial cultures with neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody and D+2-amino-5-phosphonopentanoic acid, a competitive antagonist at the N-methyl-D-aspartate/ glutamate receptor, partially protected oligodendrocytes. Co-immunolabelling of oligodendrocyte markers and neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody showed that astrocytic positive processes were in close contact with oligodendrocytes and myelin in rat optic nerves and spinal cord, but far less so in other parts of the central nervous system. This suggests a bystande...

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Glutamine Synthetase and Glutamine Synthetase‐Like Protein from Human Brain

Cited by 29 publications

References 31 publications

Systemic Neurochemical Alterations in Schizophrenic Brain: Glutamate Metabolism in Focus

Systemic Neurochemical Alterations in Schizophrenic Brain: Glutamate Metabolism in Focus

Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia

Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury

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