Evidence map›Paper›PMID 38887871›Full record

ArticleJournal of extracellular vesicles2024

Microglial activation induces nitric oxide signalling and alters protein S-nitrosylation patterns in extracellular vesicles.

Natasha Vassileff, Jereme G Spiers, Sarah E Bamford, Rohan G T Lowe, Keshava K Datta, Paul J Pigram, Andrew F Hill

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of extracellular vesicles, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Alkaloids from In Vitro CulturedPlants (Basel, Switzerland) · 2026
    Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
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.

Natasha VassileffThe Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.ORCID https://orcid.org/0000-0001-6554-4496
Jereme G SpiersThe Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.ORCID https://orcid.org/0000-0001-5872-8983
Sarah E BamfordCentre for Materials and Surface Science and Department of Mathematical and Physical Sciences, La Trobe University, Bundoora, Victoria, Australia.
Rohan G T LoweLa Trobe University Proteomics and Metabolomics Platform, La Trobe University, Bundoora, Victoria, Australia.
Keshava K DattaLa Trobe University Proteomics and Metabolomics Platform, La Trobe University, Bundoora, Victoria, Australia.
Paul J PigramCentre for Materials and Surface Science and Department of Mathematical and Physical Sciences, La Trobe University, Bundoora, Victoria, Australia.ORCID https://orcid.org/0000-0002-7972-492X
Andrew F HillThe Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.ORCID https://orcid.org/0000-0001-5581-2354

Funding

Bethlehem Griffiths Research Foundation BGRF2105National Health and Medical Research Council GNT1132604Office of National Intelligence NI210100127
6 · The paper itself

Abstract

Neuroinflammation is an underlying feature of neurodegenerative conditions, often appearing early in the aetiology of a disease. Microglial activation, a prominent initiator of neuroinflammation, can be induced through lipopolysaccharide (LPS) treatment resulting in expression of the inducible form of nitric oxide synthase (iNOS), which produces nitric oxide (NO). NO post-translationally modifies cysteine thiols through S-nitrosylation, which can alter function of the target protein. Furthermore, packaging of these NO-modified proteins into extracellular vesicles (EVs) allows for the exertion of NO signalling in distant locations, resulting in further propagation of the neuroinflammatory phenotype. Despite this, the NO-modified proteome of activated microglial EVs has not been investigated. This study aimed to identify the protein post-translational modifications NO signalling induces in neuroinflammation. EVs isolated from LPS-treated microglia underwent mass spectral surface imaging using time of flight-secondary ion mass spectrometry (ToF-SIMS), in addition to iodolabelling and comparative proteomic analysis to identify post-translation S-nitrosylation modifications. ToF-SIMS imaging successfully identified cysteine thiol side chains modified through NO signalling in the LPS treated microglial-derived EV proteins. In addition, the iodolabelling proteomic analysis revealed that the EVs from LPS-treated microglia carried S-nitrosylated proteins indicative of neuroinflammation. These included known NO-modified proteins and those associated with LPS-induced microglial activation that may play an essential role in neuroinflammatory communication. Together, these results show activated microglia can exert broad NO signalling changes through the selective packaging of EVs during neuroinflammation.

Indexed as

Extracellular VesiclesLipopolysaccharidesMicrogliaNitric OxideSignal TransductionAnimalsCysteineMiceNitric Oxide Synthase Type IIProtein Processing, Post-TranslationalProteomicsCysteineLipopolysaccharidesNitric OxideNitric Oxide Synthase Type IIextracellular vesiclesmass Spectral ImagingMicrogliaNeuroinflammationNitric OxideNitrosylationPost‐translational modificationProteomicsToF‐SIMS

Identifiers

PMID38887871
PMCPMC11183937

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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.