Evidence map›Paper›PMID 33428668›Full record

ArticlePloS one2021

Platelets express adaptor proteins of the extrinsic apoptosis pathway and can activate caspase-8.

Nadine Goelz, Julia J M Eekels, Milica Pantic, Christoph T Kamber, Oliver Speer, Francesca D Franzoso, Markus Schmugge

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword.International journal of molecular sciences · 2021
    Review
  7. 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

7 authors at 2 institutions in 2 countries.

Nadine GoelzDivision of Haematology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Julia J M EekelsDivision of Transfusion Medicine, University Hospital Greifswald, Greifswald, Germany.
Milica PanticDivision of Haematology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Christoph T KamberDivision of Haematology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Oliver SpeerInstitute for Laboratory Medicine, Hospital Thurgau AG, Münsterlingen, Switzerland.
Francesca D FranzosoDivision of Haematology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.ORCID 0000-0002-1939-376X
Markus SchmuggeDivision of Haematology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
University Children's Hospital Zurich · CHUniversitätsmedizin Greifswald · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundApoptotic pathways in platelets are important for their survival and function. Platelet apoptosis may be involved in the pathogenesis of immune thrombocytopenia (ITP), an autoimmune-mediated disease. In contrast to the intrinsic apoptosis pathway, not much is known about the extrinsic pathway mechanisms in platelets.

objectivesTo investigate the expression of proteins involved in the extrinsic apoptosis pathway, including the death receptors, adaptor and regulator proteins in human platelets. To determine a possible trigger of the extrinsic apoptosis pathway in platelets.

methodsTo investigate the expression of key markers of the extrinsic pathway we used targeted immunofluorescence and flow cytometry assays. To study their expression and interaction we performed Western blotting and co-immunoprecipitation. Treated platelets with different apoptosis triggers were subjected to flow cytometry.

resultsWe could identify the protein expression of the pro-apoptotic proteins TRADD (Tumor Necrosis Factor Receptor type 1- Associated DEATH Domain protein), TRAF2/5, (TNF Associated Factor) and DEDAF (Death Effector Domain- Associated Factor), FADD (Fas-Associated protein with death domain) as well as the anti-apoptotic proteins DJ-1 (Deglycase 1) and c-FLIP in human platelets. ABT-737 treatment induced a disruption in the co-localization of DJ-1 with FADD. Platelets treated with ABT-737 showed an activation in caspase-3 and -8. The exposure to TNF (Tumor Necrosis Factor), FasL (Fas ligand), and TWEAK or to plasma derived from ITP patients, did not lead to changes in caspase-3 and -8 activation in platelets.

conclusionsHuman platelets express some proteins of the extrinsic apoptosis pathway which can be modulated only by ABT-737 treatment. However so far, no other apoptosis trigger or interaction with an external receptor have been yet identified.

Indexed as

ApoptosisGene Expression RegulationBlood PlateletsCaspase 8ChildEnzyme ActivationFas-Associated Death Domain ProteinFemaleHumansMaleProtein Deglycase DJ-1Protein TransportCaspase 8FADD protein, humanFas-Associated Death Domain ProteinPARK7 protein, humanProtein Deglycase DJ-1

Identifiers

PMID33428668
PMCPMC7799768
OpenAlexW3120718444

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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.