glutaminase and Inflammation

glutaminase has been researched along with Inflammation* in 11 studies

Reviews

2 review(s) available for glutaminase and Inflammation

ArticleYear
[New concepts in the physiopathology of hepatic encephalopathy and therapeutic prospects].
    Gastroenterologia y hepatologia, 2004, Volume: 27 Suppl 1

    Topics: Ammonia; Brain; Brain Edema; Dipeptides; Flumazenil; Glutaminase; Glutamine; Hepatic Encephalopathy; Humans; Hyperammonemia; Inflammation; Intestine, Small; Kidney; Memantine; Models, Molecular; Nerve Tissue Proteins; Nitric Oxide

2004
Glutaminase and the control of airway pH: yet another problem for the asthmatic lung?
    American journal of respiratory and critical care medicine, 2002, Jan-01, Volume: 165, Issue:1

    Topics: Ammonia; Animals; Anti-Inflammatory Agents; Asthma; Breath Tests; Case-Control Studies; Glutaminase; Glutamine; Humans; Hydrogen-Ion Concentration; Inflammation; Rats; Respiratory Mucosa; Steroids; Up-Regulation

2002

Other Studies

9 other study(ies) available for glutaminase and Inflammation

ArticleYear
Golexanolone, a GABA
    CNS neuroscience & therapeutics, 2022, Volume: 28, Issue:11

    Hyperammonemic rats show peripheral inflammation, increased GABAergic neurotransmission and neuroinflammation in cerebellum and hippocampus which induce motor incoordination and cognitive impairment. Neuroinflammation enhances GABAergic neurotransmission in cerebellum by enhancing the TNFR1-glutaminase-GAT3 and TNFR1-CCL2-TrkB-KCC2 pathways. Golexanolone reduces GABA. Rats were treated with golexanolone and effects on peripheral inflammation, neuroinflammation, TNFR1-glutaminase-GAT3 and TNFR1-CCL2-TrkB-KCC2 pathways, and cognitive and motor function were analyzed.. Hyperammonemic rats show increased TNFα and reduced IL-10 in plasma, microglia and astrocytes activation in cerebellum and hippocampus, and impaired motor coordination and spatial and short-term memories. Treating hyperammonemic rats with golexanolone reversed changes in peripheral inflammation, microglia and astrocytes activation and restored motor coordination and spatial and short-term memory. This was associated with reversal of the hyperammonemia-enhanced activation in cerebellum of the TNFR1-glutaminase-GAT3 and TNFR1-CCL2-TrkB-KCC2 pathways.. Reducing GABA

    Topics: Animals; Cognition; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Glutaminase; Hyperammonemia; Inflammation; Interleukin-10; Neuroinflammatory Diseases; Pregnanolone; Rats; Rats, Wistar; Receptors, GABA-A; Receptors, Tumor Necrosis Factor, Type I; Symporters; Tumor Necrosis Factor-alpha

2022
Rutin prevents seizures in kainic acid-treated rats: evidence of glutamate levels, inflammation and neuronal loss modulation.
    Food & function, 2022, Oct-17, Volume: 13, Issue:20

    Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Amino Acid Transport Systems; Animals; Anti-Inflammatory Agents; Carbamazepine; Glutamate-Ammonia Ligase; Glutamic Acid; Glutaminase; Hippocampus; HMGB1 Protein; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; Kainic Acid; N-Methylaspartate; Rats; Receptors, Interleukin-1; Rutin; Seizures; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

2022
Glutaminase 1 Regulates Neuroinflammation After Cerebral Ischemia Through Enhancing Microglial Activation and Pro-Inflammatory Exosome Release.
    Frontiers in immunology, 2020, Volume: 11

    Cerebral ischemia induces a robust neuroinflammatory response that is largely mediated by the activation of CNS resident microglia. Activated microglia produce pro-inflammatory molecules to cause neuronal damage. Identifying regulators of microglial activation bears great potential in discovering promising candidates for neuroprotection post cerebral ischemia. Previous studies demonstrate abnormal elevation of glutaminase 1 (GLS1) in microglia in chronic CNS disorders including Alzheimer's disease and HIV-associated neurocognitive disorders. Ectopic expression of GLS1 induced microglia polarization into pro-inflammatory phenotype and exosome release

    Topics: Animals; Brain Ischemia; Exosomes; Glutaminase; Inflammation; Microglia; Rats; Rats, Sprague-Dawley

2020
JHU-083 selectively blocks glutaminase activity in brain CD11b
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019, Volume: 44, Issue:4

    There are a number of clinically effective treatments for stress-associated psychiatric diseases, including major depressive disorder (MDD). Nonetheless, many patients exhibit resistance to first-line interventions calling for novel interventions based on pathological mechanisms. Accumulating evidence implicates altered glutamate signaling in MDD pathophysiology, suggesting that modulation of glutamate signaling cascades may offer novel therapeutic potential. Here we report that JHU-083, our recently developed prodrug of the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine (DON) ameliorates social avoidance and anhedonia-like behaviors in mice subjected to chronic social defeat stress (CSDS). JHU-083 normalized CSDS-induced increases in glutaminase activity specifically in microglia-enriched CD11b

    Topics: Animals; Behavior, Animal; CD11b Antigen; Depression; Diazooxonorleucine; Disease Models, Animal; Glutaminase; Hippocampus; Inflammation; Male; Mice; Mice, Inbred C57BL; Prefrontal Cortex; Prodrugs; Signal Transduction; Stress, Psychological

2019
Increasing extracellular cGMP in cerebellum in vivo reduces neuroinflammation, GABAergic tone and motor in-coordination in hyperammonemic rats.
    Brain, behavior, and immunity, 2018, Volume: 69

    Hyperammonemia is a main contributor to cognitive impairment and motor in-coordination in patients with hepatic encephalopathy. Hyperammonemia-induced neuroinflammation mediates the neurological alterations in hepatic encephalopathy. Intracerebral administration of extracellular cGMP restores some but not all types of cognitive impairment. Motor in-coordination, is mainly due to increased GABAergic tone in cerebellum. We hypothesized that extracellular cGMP would restore motor coordination in hyperammonemic rats by normalizing GABAergic tone in cerebellum and that this would be mediated by reduction of neuroinflammation. The aims of this work were to assess whether chronic intracerebral administration of cGMP to hyperammonemic rats: 1) restores motor coordination; 2) reduces neuroinflammation in cerebellum; 3) reduces extracellular GABA levels and GABAergic tone in cerebellum; and also 4) to provide some advance in the understanding on the molecular mechanisms involved. The results reported show that rats with chronic hyperammonemia show neuroinflammation in cerebellum, including microglia and astrocytes activation and increased levels of IL-1b and TNFa and increased membrane expression of the TNFa receptor. This is associated with increased glutaminase expression and extracellular glutamate, increased amount of the GABA transporter GAT-3 in activated astrocytes, increased extracellular GABA in cerebellum and motor in-coordination. Chronic intracerebral administration of extracellular cGMP to rats with chronic hyperammonemia reduces neuroinflammation, including microglia and astrocytes activation and membrane expression of the TNFa receptor. This is associated with reduced nuclear NF-κB, glutaminase expression and extracellular glutamate, reduced amount of the GABA transporter GAT-3 in activated astrocytes and reduced extracellular GABA in cerebellum and restoration of motor coordination. The data support that extracellular cGMP restores motor coordination in hyperammonemic rats by reducing microglia activation and neuroinflammation, leading to normalization of extracellular glutamate and GABA levels in cerebellum and of motor coordination.

    Topics: Animals; Astrocytes; Bicuculline; Cerebellum; Cyclic GMP; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Glutaminase; Hyperammonemia; Inflammation; Male; Microglia; Motor Skills; Rats; Rats, Wistar

2018
TNF-α promotes extracellular vesicle release in mouse astrocytes through glutaminase.
    Journal of neuroinflammation, 2017, 04-20, Volume: 14, Issue:1

    Extracellular vesicles (EVs) are membrane-contained vesicles shed from cells. EVs contain proteins, lipids, and nucleotides, all of which play important roles in intercellular communication. The release of EVs is known to increase during neuroinflammation. Glutaminase, a mitochondrial enzyme that converts glutamine to glutamate, has been implicated in the biogenesis of EVs. We have previously demonstrated that TNF-α promotes glutaminase expression in neurons. However, the expression and the functionality of glutaminase in astrocytes during neuroinflammation remain unknown. We posit that TNF-α can promote the release of EVs in astrocytes through upregulation of glutaminase expression.. Release of EVs, which was demonstrated by electron microscopy, nanoparticle tracking analysis (NTA), and Western Blot, increased in mouse astrocytes when treated with TNF-α. Furthermore, TNF-α treatment significantly upregulated protein levels of glutaminase and increased the production of glutamate, suggesting that glutaminase activity is increased after TNF-α treatment. Interestingly, pretreatment with a glutaminase inhibitor blocked TNF-α-mediated generation of reactive oxygen species in astrocytes, which indicates that glutaminase activity contributes to stress in astrocytes during neuroinflammation. TNF-α-mediated increased release of EVs can be blocked by either the glutaminase inhibitor, antioxidant N-acetyl-L-cysteine, or genetic knockout of glutaminase, suggesting that glutaminase plays an important role in astrocyte EV release during neuroinflammation.. These findings suggest that glutaminase is an important metabolic factor controlling EV release from astrocytes during neuroinflammation.

    Topics: Animals; Astrocytes; Cells, Cultured; Extracellular Vesicles; Glutaminase; Inflammation; Mice; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Up-Regulation

2017
Peripheral inhibition of glutaminase reduces carrageenan-induced Fos expression in the superficial dorsal horn of the rat.
    Neuroscience letters, 2010, Mar-26, Volume: 472, Issue:3

    In inflamed tissue, the levels of the excitatory amino acid glutamate are increased. Glutamate sensitizes peripheral axons of primary afferent neurons during inflammation leading to decreased firing threshold and hyperexcitability. One proposed source of glutamate is the primary afferent. Antagonizing glutamate receptors on peripheral axons of primary afferents during inflammation provides analgesia in animals and humans. The enzyme glutaminase is used by primary sensory neurons to convert glutamine to glutamate, and peripheral inhibition of glutaminase with 6-diazo-5-oxo-l-norleucine (DON) provides long-lasting analgesia during inflammation. In this study, we measured the effects of glutaminase inhibition on carrageenan-induced spinal Fos expression. Rats were given intraplantar injections of carrageenan and treated locally with either vehicle or DON. After 3h of inflammation, hind paw swelling and spinal expression of Fos were examined. CellProfiler was used to automate Fos nuclei counting in five laminar groupings in the spinal cord (I-II, III-IV, V-VI, VII-IX, X). Carrageenan increased hind paw thickness by approximately 70% and spinal Fos expression in superficial (I-II) and deep (V-VI) laminae by 10-fold and 5-fold, respectively. Treatment with DON reduced hind paw swelling by approximately 13% and suppressed Fos expression in the laminae I-II by approximately 54%, but not the deep laminae. Our results further support the notion of glutamate as a peripheral inflammatory mediator and indicate that glutaminase should be considered as a novel therapeutic target for treatment of inflammatory pain.

    Topics: Analgesics; Animals; Carrageenan; Diazooxonorleucine; Edema; Glutamic Acid; Glutaminase; Inflammation; Nerve Endings; Posterior Horn Cells; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Spinal Cord

2010
Expression and activity of pH-regulatory glutaminase in the human airway epithelium.
    American journal of respiratory and critical care medicine, 2002, Jan-01, Volume: 165, Issue:1

    Fluid condensed from the breath of patients with acute asthma is acidic. Several features of asthma pathophysiology can be initiated by exposure of the airway to acid. In renal tubular epithelium, glutaminase produces ammonia to buffer urinary acid excretion. We hypothesized that human airway epithelium could also express glutaminase. Here, we demonstrate that human airway epithelial cells in vitro have biochemical evidence for glutaminase activity and express mRNA for two glutaminase isoforms (KGA and GAC). Glutaminase activity increased in response to acidic stress (media pH 5.8) and was associated with both increased culture medium pH and improved cell survival. In contrast, activity was inhibited by interferon-gamma and tumor necrosis factor-alpha. Glutaminase protein was expressed in the human airway in vivo. Further, ammonia levels in the breath condensate of subjects with acute asthma were low (30 microM [range: 0-233], n = 18, age 23 +/- 2.5 yr) compared with control subjects (327 microM [14-1,220], n = 24, age 24 +/- 2.4 yr, p < 0.001), and correlated with condensate pH (r = 0.58, p < 0.001). These data demonstrate that glutaminase is expressed and active in the human airway epithelium and may be relevant both to the regulation of airway pH and to the pathophysiology of acute asthmatic airway inflammation.

    Topics: Acute Disease; Adult; Ammonia; Analysis of Variance; Asthma; Biopsy; Blotting, Western; Breath Tests; Case-Control Studies; Cell Survival; Gene Expression Regulation; Glutaminase; Humans; Hydrogen-Ion Concentration; Immunohistochemistry; Inflammation; Interferon-gamma; Isomerism; Respiratory Mucosa; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Up-Regulation

2002
Enzymes of glutamine metabolism in inflammation associated with skeletal muscle hypertrophy.
    The American journal of physiology, 1989, Volume: 257, Issue:6 Pt 1

    Glutamine synthesis and utilization were studied in the plantaris muscle after removal of its functional synergists, the soleus and gastrocnemius muscles. Rat plantaris muscle was compared with unoperated controls at 7, 14, and 30 days after synergist ablation and induction of hypertrophy. Glutamine synthetase activity increased from 6.17 +/- 1.77 to 33.92 +/- 2.23 nmol.h-1.mg protein-1, and glutaminase activities increased from 98.63 +/- 23.05 to 478.70 +/- 64.17 nmol.h-1.mg protein-1 7 days after surgery and remained elevated at 14 and 30 days. Sham-operated controls examined 7 days after surgery did not exhibit significantly increased glutamine synthetase activity. Histological examination revealed a large proliferation of connective tissue cells, as well as cells involved in tissue repair and inflammation; this influx was maximal 1 wk after surgery. The activity of the oxidative enzymes of the pentose phosphate pathway increased from 3.08 +/- 4.31 to 20.86 +/- 1.13 nmol.min-1.mg protein-1 1 wk after surgery. The time course of changes in pentose phosphate pathway enzymes was similar to that of the increases in glutamine synthetase, glutaminase, and cellular infiltration. Increases in muscle wet weight followed a different time course than changes in glutamine synthetase, glutaminase, and pentose phosphate pathway activities. It is concluded that the initial increases in plantaris muscle weight are probably due to edema, connective tissue proliferation, and cells involved in tissue repair and inflammation. The increase in glutamine synthetase activity appears to occur in skeletal muscle, whereas the changes in glutaminase and pentose phosphate pathway activities appear to represent infiltrating inflammatory cells. Furthermore, the increase in glutamine synthetase activity may serve to support the infiltrating cells, which appear to lack substantial capacity for glutamine production. These results represent a functional relationship between skeletal muscle glutamine synthesis and utilization by cells mediating inflammation and connective tissue repair and synthesis.

    Topics: Animals; Glutamate-Ammonia Ligase; Glutaminase; Glutamine; Hypertrophy; Inflammation; Male; Microscopy, Electron; Muscles; Pentose Phosphate Pathway; Rats; Rats, Inbred Strains; Reference Values

1989