Evidence map›Paper›PMID 22815910›Full record

ArticlePloS one2012

Vitamin E isoforms differentially regulate intercellular adhesion molecule-1 activation of PKCα in human microvascular endothelial cells.

Hiam Abdala-Valencia, Sergejs Berdnikovs, Joan M Cook-Mills

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

25 citing papers in PubMed, 44 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. The Role of Vitamins in the Pathogenesis of Asthma.International journal of molecular sciences · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Roles of vitamins in stem cells.Cellular and molecular life sciences : CMLS · 2020
    Review
  10. Article
  11. Review
  12. Oxidative Stress: Harms and Benefits for Human Health.Oxidative medicine and cellular longevity · 2017
    Review
  13. Article
  14. Article
  15. Review
  16. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015
    Article
  17. Article
  18. Review
  19. Article
  20. Review
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

3 authors at 1 institution in 1 country.

Hiam Abdala-ValenciaAllergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Sergejs Berdnikovs
Joan M Cook-Mills
Northwestern University · US

Funding

Forms of Vitamin E Have Opposing Effects on InflammationR01AT004837 · NCCIH · NORTHWESTERN UNIVERSITY AT CHICAGO · PI COOK-MILLS, JOAN M · 2008 to 2011
$1.5M
NCCIH NIH HHS R01 AT004837
6 · The paper itself

Abstract

aimsICAM-1-dependent leukocyte recruitment in vivo is inhibited by the vitamin E isoform d-α-tocopherol and elevated by d-γ-tocopherol. ICAM-1 is reported to activate endothelial cell signals including protein kinase C (PKC), but the PKC isoform and the mechanism for ICAM-1 activation of PKC are not known. It is also not known whether ICAM-1 signaling in endothelial cells is regulated by tocopherol isoforms. We hypothesized that d-α-tocopherol and d-γ-tocopherol differentially regulate ICAM-1 activation of endothelial cell PKC.

resultsICAM-1 crosslinking activated the PKC isoform PKCα but not PKCβ in TNFα-pretreated human microvascular endothelial cells. ICAM-1 activation of PKCα was blocked by the PLC inhibitor U73122, ERK1/2 inhibitor PD98059, and xanthine oxidase inhibitor allopurinol. ERK1/2 activation was blocked by inhibition of XO and PLC but not by inhibition of PKCα, indicating that ERK1/2 is downstream of XO and upstream of PKCα during ICAM-1 signaling. During ICAM-1 activation of PKCα, the XO-generated ROS did not oxidize PKCα. Interestingly, d-α-tocopherol inhibited ICAM-1 activation of PKCα but not the upstream signal ERK1/2. The d-α-tocopherol inhibition of PKCα was ablated by the addition of d-γ-tocopherol.

conclusionsCrosslinking ICAM-1 stimulated XO/ROS which activated ERK1/2 that then activated PKCα. ICAM-1 activation of PKCα was inhibited by d-α-tocopherol and this inhibition was ablated by the addition of d-γ-tocopherol. These tocopherols regulated ICAM-1 activation of PKCα without altering the upstream signal ERK1/2. Thus, we identified a mechanism for ICAM-1 activation of PKC and determined that d-α-tocopherol and d-γ-tocopherol have opposing regulatory functions for ICAM-1-activated PKCα in endothelial cells.

Indexed as

Gene Expression Regulation, EnzymologicCysteineEndothelial CellsExtracellular Signal-Regulated MAP KinasesHumansIntercellular Adhesion Molecule-1LungMicrocirculationOxygenPhosphorylationProtein IsoformsProtein Kinase C-alphaVitamin EXanthine OxidaseCysteineExtracellular Signal-Regulated MAP KinasesIntercellular Adhesion Molecule-1OxygenProtein IsoformsProtein Kinase C-alphaVitamin EXanthine Oxidase

Identifiers

PMID22815910
PMCPMC3398863
OpenAlexW2053647141

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.