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Reactive Metabolite-induced Protein Glutathionylation: A Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity

Overview of attention for article published in Molecular and Cellular Proteomics, July 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#5 of 2,284)
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (88th percentile)

Mentioned by

news
12 news outlets
twitter
17 tweeters

Citations

dimensions_citation
1 Dimensions

Readers on

mendeley
5 Mendeley
Title
Reactive Metabolite-induced Protein Glutathionylation: A Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity
Published in
Molecular and Cellular Proteomics, July 2018
DOI 10.1074/mcp.ra118.000875
Pubmed ID
Authors

James Chun Yip Chan, Alex Cheow Khoon Soh, Dorinda Yan Qin Kioh, Jianguo Li, Chandra Verma, Siew Kwan Koh, Roger Wilmer Beuerman, Lei Zhou, Eric Chun Yong Chan

Abstract

Although covalent protein binding is established as the pivotal event underpinning acetaminophen (APAP) toxicity, its mechanistic details remain unclear. In this study, we demonstrated that APAP induces widespread protein glutathionylation in a time-, dose- and bioactivation-dependent manner in HepaRG cells. Proteo-metabonomic mapping provided evidence that APAP-induced glutathionylation resulted in functional deficits in energy metabolism, elevations in oxidative stress and cytosolic calcium, as well as mitochondrial dysfunction that correlate strongly with the well-established toxicity features of APAP. We also provide novel evidence that APAP-induced glutathionylation of carnitine O-palmitoyltransferase 1 (CPT1) and voltage-dependent anion-selective channel protein 1 are respectively involved in inhibition of fatty acid β-oxidation and opening of the mitochondrial permeability transition pore. Importantly, we show that the inhibitory effect of CPT1 glutathionylation can be mitigated by PPARα induction, which provides a mechanistic explanation for the prophylactic effect of fibrates, which are PPARα ligands, against APAP toxicity. Finally, we propose that APAP-induced protein glutathionylation likely occurs secondary to covalent binding, which is a previously unknown mechanism of glutathionylation, suggesting that this post-translational modification could be functionally implicated in drug-induced toxicity.

Twitter Demographics

The data shown below were collected from the profiles of 17 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 20%
Unknown 4 80%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 80%
Student > Master 2 40%
Researcher 1 20%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 2 40%
Computer Science 1 20%
Biochemistry, Genetics and Molecular Biology 1 20%
Agricultural and Biological Sciences 1 20%
Psychology 1 20%
Other 1 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 104. 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 02 November 2018.
All research outputs
#123,300
of 12,119,749 outputs
Outputs from Molecular and Cellular Proteomics
#5
of 2,284 outputs
Outputs of similar age
#5,888
of 244,003 outputs
Outputs of similar age from Molecular and Cellular Proteomics
#1
of 9 outputs
Altmetric has tracked 12,119,749 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,284 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one has done particularly well, scoring higher than 99% 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 244,003 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them