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Glutamate metabolism in HIV-1 infected macrophages: Role of HIV-1 Vpr

Overview of attention for article published in Cell Cycle, August 2016
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  • High Attention Score compared to outputs of the same age and source (95th percentile)

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Title
Glutamate metabolism in HIV-1 infected macrophages: Role of HIV-1 Vpr
Published in
Cell Cycle, August 2016
DOI 10.1080/15384101.2016.1190054
Pubmed ID
Authors

Prasun K. Datta, Satish Deshmane, Kamel Khalili, Salim Merali, John C. Gordon, Chiara Fecchio, Carlos A. Barrero

Abstract

HIV-1 infected macrophages play a significant role in the neuropathogenesis of AIDS. HIV-1 viral protein R (Vpr) not only facilitates HIV-1 infection but also contribute to long-lived persistence in macrophages. Our previous studies using SILAC-based proteomic analysis showed that the expression of critical metabolic enzymes in the glycolytic pathway and tricarboxylic acid (TCA) cycle were altered in response to Vpr expression in macrophages. We hypothesized that Vpr-induced modulation of glycolysis and TCA cycle regulates glutamate metabolism and release in HIV-1 infected macrophages. We assessed the amount of specific metabolites induced by Vpr and HIV-1 in macrophages at the intracellular and extracellular level in a time-dependent manner utilizing multiple reaction monitoring (MRM) targeted metabolomics. In addition, stable isotope-labeled glucose and an MRM targeted metabolomics assay were used to evaluate the de novo synthesis and release of glutamate in Vpr overexpressing macrophages and HIV-1 infected macrophages, throughout the metabolic flux of glycolytic pathway and TCA cycle activation. The metabolic flux studies demonstrated an increase in glucose uptake, glutamate release and accumulation of α-ketoglutarate (α-KG) and glutamine in the extracellular milieu in Vpr expressing and HIV-1 infected macrophages. Interestingly, glutamate pools and other intracellular intermediates (glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), citrate, malate, α-KG, and glutamine) showed a decreased trend except for fumarate, in contrast to the glutamine accumulation observed in the extracellular space in Vpr overexpressing macrophages. Our studies demonstrate that dysregulation of mitochondrial glutamate metabolism induced by Vpr in HIV-1 infected macrophages commonly seen, may contribute to neurodegeneration via excitotoxic mechanisms in the context of NeuroAIDS.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 59 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 17%
Researcher 9 15%
Student > Master 7 12%
Student > Doctoral Student 4 7%
Student > Bachelor 3 5%
Other 6 10%
Unknown 20 34%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 24%
Agricultural and Biological Sciences 6 10%
Medicine and Dentistry 6 10%
Immunology and Microbiology 5 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 5 8%
Unknown 21 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 March 2023.
All research outputs
#6,368,979
of 23,495,502 outputs
Outputs from Cell Cycle
#660
of 3,721 outputs
Outputs of similar age
#104,161
of 358,229 outputs
Outputs of similar age from Cell Cycle
#5
of 107 outputs
Altmetric has tracked 23,495,502 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 3,721 research outputs from this source. They receive a mean Attention Score of 3.7. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 358,229 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 107 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.