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Metabolomics Based Identification of SIRT5 and Protein Kinase C Epsilon Regulated Pathways in Brain

Overview of attention for article published in Frontiers in Neuroscience, January 2018
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Title
Metabolomics Based Identification of SIRT5 and Protein Kinase C Epsilon Regulated Pathways in Brain
Published in
Frontiers in Neuroscience, January 2018
DOI 10.3389/fnins.2018.00032
Pubmed ID
Authors

Kevin B. Koronowski, Nathalie Khoury, Kahlilia C. Morris-Blanco, Holly M. Stradecki-Cohan, Timothy J. Garrett, Miguel A. Perez-Pinzon

Abstract

The role of Sirtuins in brain function is emerging, yet little is known about SIRT5 in this domain. Our previous work demonstrates that protein kinase C epsilon (PKCε)-induced protection from focal ischemia is lost in SIRT5-/-mice. Thus, metabolic regulation by SIRT5 contributes significantly to ischemic tolerance. The aim of this study was to identify the SIRT5-regulated metabolic pathways in the brain and determine which of those pathways are linked to PKCε. Our results show SIRT5 is primarily expressed in neurons and endothelial cells in the brain, with mitochondrial and extra-mitochondrial localization. Pathway and enrichment analysis of non-targeted primary metabolite profiles from Sirt5-/-cortex revealed alterations in several pathways including purine metabolism (urea, adenosine, adenine, xanthine), nitrogen metabolism (glutamic acid, glycine), and malate-aspartate shuttle (malic acid, glutamic acid). Additionally, perturbations in β-oxidation and carnitine transferase (pentadecanoic acid, heptadecanoic acid) and glutamate transport and glutamine synthetase (urea, xylitol, adenine, adenosine, glycine, glutamic acid) were predicted. Metabolite changes in SIRT5-/-coincided with alterations in expression of amino acid (SLC7A5, SLC7A7) and glutamate (EAAT2) transport proteins as well as key enzymes in purine (PRPS1, PPAT), fatty acid (ACADS, HADHB), glutamine-glutamate (GAD1, GLUD1), and malate-aspartate shuttle (MDH1) metabolic pathways. Moreover, PKCε activation induced alternations in purine metabolites (urea, glutamine) that overlapped with putative SIRT5 pathways in WT but not in SIRT5-/-mice. Finally, we found that purine metabolism is a common metabolic pathway regulated by SIRT5, PKCε and ischemic preconditioning. These results implicate Sirt5 in the regulation of pathways central to brain metabolism, with links to ischemic tolerance.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 23%
Student > Master 7 23%
Student > Bachelor 3 10%
Professor > Associate Professor 3 10%
Other 2 7%
Other 4 13%
Unknown 4 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 27%
Agricultural and Biological Sciences 6 20%
Medicine and Dentistry 2 7%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Sports and Recreations 1 3%
Other 3 10%
Unknown 9 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 01 February 2018.
All research outputs
#20,663,600
of 25,382,440 outputs
Outputs from Frontiers in Neuroscience
#9,459
of 11,542 outputs
Outputs of similar age
#343,365
of 449,219 outputs
Outputs of similar age from Frontiers in Neuroscience
#184
of 214 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 214 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.