Evidence map›Paper›PMID 18624925›Full record

ArticleJournal of neurochemistry2008

Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: the role of NADPH oxidases.

Timothy J Harrigan, Iskandar F Abdullaev, David Jourd'heuil, Alexander A Mongin

Abstract read
In one paragraph

Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
4.3field-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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Timothy J HarriganCenter for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.
Iskandar F Abdullaev
David Jourd'heuil
Alexander A Mongin
Albany Medical Center Hospital · US

Funding

PHARMACOLOGY &NEUROSCIENCE TRAINING IN DRUG ABUSET32DA007307 · NIDA · ALBANY MEDICAL COLLEGE · PI GLICK, STANLEY D · 1999 to 2008
$1.8M
NIDA NIH HHS T32 DA007307
6 · The paper itself

Abstract

Microglia are the resident immune cells of the CNS, which are important for preserving neural tissue functions, but may also contribute to neurodegeneration. Activation of these cells in infection, inflammation, or trauma leads to the release of various toxic molecules, including reactive oxygen species (ROS) and the excitatory amino acid glutamate. In this study, we used an electrophysiologic approach and a D-[(3)H]aspartate (glutamate) release assay to explore the ROS-dependent regulation of glutamate-permeable volume-regulated anion channels (VRACs). Exposure of rat microglia to hypo-osmotic media stimulated Cl(-) currents and D-[(3)H]aspartate release, both of which were inhibited by the selective VRAC blocker, DCPIB. Exogenously applied H(2)O(2) potently increased swelling-activated glutamate release. Stimulation of microglia with zymosan triggered production of endogenous ROS and strongly enhanced glutamate release via VRAC in swollen cells. The effects of zymosan were attenuated by the ROS scavenger, MnTMPyP, and by two inhibitors of NADPH oxidase (NOX), diphenyliodonium and thioridazine. However, zymosan-stimulated glutamate release was insensitive to other NOX blockers, apocynin and HEBSF. This pharmacologic profile pointed to the potential involvement of apocynin-insensitive NOX4. Using RT-PCR we confirmed that NOX4 is expressed in rat microglial cells along with NOX1 and NOX2. To check for potential involvement of phagocytic NOX2, we stimulated this isoform using protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate or inhibited it with the broad spectrum PKC blocker, Gö6983. Both agents potently modulated endogenous ROS production by NOX2 but not VRAC activity. Taken together, these data suggest that the anion channel VRAC may contribute to microglial glutamate release and that its activity is regulated by endogenous ROS originating from NOX4.

Indexed as

AnimalsAnimals, NewbornAspartic AcidCells, CulturedEncephalitisEnzyme InhibitorsExcitatory Amino AcidsGlutamic AcidIsoenzymesMicrogliaNADPH Oxidase 4NADPH OxidasesOxidantsOxidative StressProtein Kinase CRatsAspartic AcidEnzyme InhibitorsExcitatory Amino AcidsGlutamic AcidIsoenzymesNADPH Oxidase 4NADPH OxidasesNox4 protein, ratOxidantsProtein Kinase CReactive Oxygen SpeciesVoltage-Dependent Anion ChannelsZymosan

Identifiers

PMID18624925
PMCPMC2574595
OpenAlexW2000397596

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.