Mitochondrial glutaminase enhances extracellular glutamate production in HIV‐1‐infected macrophages: Linkage to HIV‐1 associated dementia

Zhao, Jian; López, Alicia; Erichsen, David; Herek, Shelley; Cotter, Robin L.; Curthoys, Norman P.; Zheng, Jialin

doi:10.1046/j.1471-4159.2003.02146.x

Cited by 98 publications

(134 citation statements)

References 47 publications

(113 reference statements)

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“…This enzyme gained importance in industrial and pharmaceutical sectors as an effective therapeutic agent in the treatment of HIV (16,27) and acute lymphocytic leukaemia (22). The enzyme causes selective death of glutaminedependent tumor cells by depriving these cells of glutamine.…”

Section: Microbial L-glutaminases or Glutaminases (L-mentioning

confidence: 99%

Medium optimization for production of L-Glutaminase (EC 3.5.1.2) by Streptomyces griseus under submerged fermentation

Suresh¹,

Muthuvelayudham²,

Viruthagiri³

2013

IJSEA

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L-Glutaminase is widely distributed in microorganisms including bacteria, yeast and fungi. The enzyme mainly catalyzes the hydrolysis of γ-amido bond of l-glutamine. In this report medium optimization was conducted through one -factor -at -a -time approach for the submerged production of L-Glutaminase by Streptomyces griseus using different additional carbon, nitrogen, amino acids, mineral salts and was treated with different concentration sodium chloride. A significant influence of medium components (g/l) Galactose 10.0,Yeast extract 10.0,L-Glutamine 10.0,Magnesium sulphate 0.5, KH 2 PO 4 0.5 , K 2 HPO 4 0.5, NaCl 40 on L-Glutaminase production was noted. The applied methodology was validated using this optimized media, the enzyme activity 45 IU/ml in 48h of incubation was obtained.

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Section: Microbial L-glutaminases or Glutaminases (L-mentioning

confidence: 99%

Medium optimization for production of L-Glutaminase (EC 3.5.1.2) by Streptomyces griseus under submerged fermentation

Suresh¹,

Muthuvelayudham²,

Viruthagiri³

2013

IJSEA

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“…Improper regulation of these factors can lead to impaired cellular functioning, modified neurotransmitter action, amplified inflammation and neuronal damage. Various potential neurotoxins are generated and released during the inflammatory process including reactive oxygen species, tumor necrosis factor-α (TNF-α), arachidonic acid, platelet-activating factor (PAF), nitric oxide, quinolinic acid, and glutamate (20,30,(46)(47)(48)(49)(50)(51)(52).…”

Section: Macrophage Driven Pathogenesismentioning

confidence: 99%

“…Glutamate is secreted in large quantities by macrophage (20,30,181). The MP cell population expresses glutaminase at significant levels (30).…”

Section: Glutaminasementioning

confidence: 99%

“…Our group recently demonstrated a glutamine dependent upregulation of glutamate production by HIV-1 infected macrophage cultures. This glutamate increase relates to cell viability, and was nearly eliminated in the presence of antiviral treatment (30). Thus, HIV-1 may lead to increased enzyme activity or release of enzyme into a glutamine rich substrate with little product feedback, allowing excess glutamate generation from macrophage populations.…”

Section: Glutaminasementioning

confidence: 99%

“…HIV-1-infected patients have been reported to have significantly higher plasma concentrations of glutamate as compared to uninfected controls (28,29). HIV-1 infected macrophages appear to be an important source of extracellular glutamate (20), this glutamate production has recently been linked to the activity of phosphate-activated mitochondrial glutaminase (30). Glutaminase catalyzes the conversion of glutamine to glutamate, is the primary enzyme for the production of glutamate in the CNS (31)(32)(33)(34) and is also the predominant glutamine-utilizing enzyme of the brain (35,36).…”

Section: Introductionmentioning

confidence: 99%

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Potentiation of excitotoxicity in HIV-1-associated Dementia and the significance of glutaminase

Erdmann¹,

Whitney²,

Zheng³

2006

Clinical Neuroscience Research

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HIV-1 Associated Dementia (HAD) is a significant consequence of HIV infection. Although multiple inflammatory factors contribute to this chronic, progressive dementia, excitotoxic damage appears to be an underlying mechanism in the neurodegenerative process. Excitotoxicity is a cumulative effect of multiple processes occurring in the CNS during HAD. The overstimulation of glutamate receptors, an increased vulnerability of neurons, and disrupted astrocyte support each potentiate excitotoxic damage to neurons. Recent evidence suggests that poorly controlled generation of glutamate by phosphate-activated glutaminase may contribute to the neurotoxic state typical of HAD as well as other neurodegenerative disorders. Glutaminase converts glutamine, a widely available substrate throughout the CNS to glutamate. Inflammatory conditions may precipitate unregulated activity of glutaminase, a potentially important mechanism in HAD pathogenesis.

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Extracellular vesicles in toxicological studies: key roles in communication between environmental stress and adverse outcomes

Qin

Huang

2020

J of Applied Toxicology

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External stressors, especially environmental toxicants can disturb biological homeostasis and thus lead to adverse health effects. However, there is limited understanding of how cells directly exposed to stressors transmit the signals to cells indirectly in contact with stressors. Extracellular vesicles (EVs) are receiving increasing attention as signal transductors between various types of cells in organisms. Cargo in EVs, including RNAs, proteins, lipids, and other signal molecules can be transferred between cells and become critical determining factors of intercellular communication. EVs can be a powerful mediator of environmental stimuli. It has been shown that external stressors reshape the secretion of EVs, modify the composition of EVs, and thus influence the mediating function of EVs. These abnormal EVs can lead to dysfunction of recipient cells, and even the pathogenesis of diseases. In this review, we first summarized current knowledge about the responses of EVs to external stimuli, including chemicals and chemical mixtures. Then we explained how these altered EVs regulate signal pathways in recipient cells, thus mediating physio‐pathological responses in detail. The most up‐to‐date evidence from molecular, cellular, animal and human levels was synthesized to systematically address the mediating roles of EVs. EVs can be regarded as a bridge to link external stressors and internal response. Further toxicological and molecular epidemiological studies are expected to provide further insight into the roles of EVs in toxicology. The gaps in the engulfment of toxicants into EVs are listed as the priority to be solved in future studies.

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Mitochondrial glutaminase enhances extracellular glutamate production in HIV‐1‐infected macrophages: Linkage to HIV‐1 associated dementia

Cited by 98 publications

References 47 publications

Medium optimization for production of L-Glutaminase (EC 3.5.1.2) by Streptomyces griseus under submerged fermentation

Medium optimization for production of L-Glutaminase (EC 3.5.1.2) by Streptomyces griseus under submerged fermentation

Potentiation of excitotoxicity in HIV-1-associated Dementia and the significance of glutaminase

Extracellular vesicles in toxicological studies: key roles in communication between environmental stress and adverse outcomes

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