Evidence map›Paper›PMID 28756226›Full record

ArticleBiochemical and biophysical research communications2017

Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications.

Santosh Kumar, Namita Sinha, Kelli A Gerth, Mohammad A Rahman, Murali M Yallapu, Narasimha M Midde

Abstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 66 citations in OpenAlex.

  1. Review
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  8. The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024
    Review
  9. Article
  10. Article
  11. Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023
    Review
  12. Review
  13. Role of Extracellular Vesicles in Liver Diseases.Life (Basel, Switzerland) · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Santosh KumarDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: ksantosh@uthsc.edu.
Namita SinhaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Kelli A GerthDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Mohammad A RahmanDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Murali M YallapuDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Narasimha M MiddeDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
University of Tennessee Health Science Center · US

Funding

Role of cytochrome P450 in alcohol-mediated effects on antiretroviral and HIV-1R01AA022063 · NIAAA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI KUMAR, SANTOSH · 2013 to 2017
$1.7M
Exosomes in tobacco-and HIV-mediated neurotoxcityR21DA042374 · NIDA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI KUMAR, SANTOSH · 2016 to 2017
$431k
NIAAA NIH HHS R01 AA022063NIDA NIH HHS R21 DA042374
6 · The paper itself

Abstract

Cytochrome P450 (CYP) enzymes metabolize the majority of xenobiotics and are mainly found in hepatic and some extra-hepatic cells. However, their presence and functional role in exosomes, small extracellular vesicles that are secreted from various cells into extracellular fluids including plasma, is unknown. In this study, we analyzed the expression and biological activity of CYP enzymes in human plasma exosomes. First, we optimized isolation of plasma exosomes and characterized them for their physical properties and quality. The results showed that the purity of exosomes (<200 nm) improved upon prior filtration of plasma using a 0.22 micron filter. We then analyzed the relative level of exosomal CYP mRNAs, proteins, and enzyme activity. The results showed that the relative level of CYP enzymes in exosomes is higher than in plasma, suggesting their specific packaging in exosomes. Of the seven CYP enzymes tested, the mRNA of CYP1B1, CYP2A6, CYP2E1, and CYP3A4 were detectable in exosomes. Interestingly, the relative level of CYP2E1 mRNA was >500-fold higher than the other CYPs. The results from the Western blot showed detectable levels of CYP1A1, CYP1B1, CYP2A6, CYP2E1, and CYP3A4. Our results also demonstrated that exosomal CYP2E1 and CYP3A4 show appreciable activity relative to their respective positive controls (CYP-induced baculosomes). Our results also showed that CYP2E1 is expressed relatively higher in plasma exosomes than hepatic and monocytic cells and exosomes derived from these cells. In conclusion, this is the first evidence of the specific packaging and circulation of CYP enzymes, especially CYP2E1, in human plasma exosomes. The findings have biological and clinical significance in terms of their implications in cellular communications and potential use of plasma exosomal CYPs as biomarkers.

Indexed as

Blood ProteinsCell CommunicationCytochrome P-450 CYP2E1Cytochrome P-450 Enzyme SystemEnzyme ActivationExosomesHumansBlood ProteinsCytochrome P-450 CYP2E1Cytochrome P-450 Enzyme SystemCYP2E1Cytochrome P450ExosomesPlasma

Identifiers

PMID28756226
PMCPMC5901973
OpenAlexW2738254383

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.