Evidence map›Paper›PMID 32502899›Full record

ArticleRedox biology2020

Astrocyte glutathione maintains endothelial barrier stability.

Sheng-Fu Huang, Alaa Othman, Alexey Koshkin, Sabrina Fischer, David Fischer, Nicola Zamboni, Katsuhiko Ono, Tomohiro Sawa, Omolara O Ogunshola

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.3field-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

36 citing papers in PubMed, 50 citations in OpenAlex.

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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

9 authors at 3 institutions in 2 countries.

Sheng-Fu HuangInstitute for Veterinary Physiology, University of Zurich, Winterthurerstrasse 260, CH-8057, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Alaa OthmanDepartment of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich, Otto-Stern-Weg 3, CH-8093, Zurich, Switzerland.
Alexey KoshkinInstitute for Veterinary Physiology, University of Zurich, Winterthurerstrasse 260, CH-8057, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Sabrina FischerInstitute for Veterinary Physiology, University of Zurich, Winterthurerstrasse 260, CH-8057, Zurich, Switzerland; Institute of Zoology, University of Basel, Vesalgasse 1, CH-4051, Basel, Switzerland.
David FischerFunctional Genomics Center Zurich, University of Zurich, Winterthurerstrasse 260, CH-8057, Zurich, Switzerland.
Nicola ZamboniDepartment of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich, Otto-Stern-Weg 3, CH-8093, Zurich, Switzerland.
Katsuhiko OnoDepartment of Microbiology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Tomohiro SawaDepartment of Microbiology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Omolara O OgunsholaInstitute for Veterinary Physiology, University of Zurich, Winterthurerstrasse 260, CH-8057, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. Electronic address: larao@access.uzh.ch.
University of Zurich · CHETH Zurich · CHKumamoto University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Blood-brain barrier (BBB) impairment clearly accelerates brain disease progression. As ways to prevent injury-induced barrier dysfunction remain elusive, better understanding of how BBB cells interact and modulate barrier integrity is needed. Our metabolomic profiling study showed that cell-specific adaptation to injury correlates well with metabolic reprogramming at the BBB. In particular we noted that primary astrocytes (AC) contain comparatively high levels of glutathione (GSH)-related metabolites compared to primary endothelial cells (EC). Injury significantly disturbed redox balance in EC but not AC motivating us to assess 1) whether an AC-EC GSH shuttle supports barrier stability and 2) the impact of GSH on EC function. Using an isotopic labeling/tracking approach combined with Time-of-Flight Mass Spectrometry (TOF-MS) we prove that AC constantly shuttle GSH to EC even under resting conditions - a flux accelerated by injury conditions in vitro. In correlation, co-culture studies revealed that blocking AC GSH generation and secretion via siRNA-mediated γ-glutamyl cysteine ligase (GCL) knockdown significantly compromises EC barrier integrity. Using different GSH donors, we further show that exogenous GSH supplementation improves barrier function by maintaining organization of tight junction proteins and preventing injury-induced tight junction phosphorylation. Thus the AC GSH shuttle is key for maintaining EC redox homeostasis and BBB stability suggesting GSH supplementation could improve recovery after brain injury.

Indexed as

AstrocytesGlutathioneBlood-Brain BarrierEndothelial CellsTight JunctionsGlutathioneBarrier stabilityBlood-brain barrierMetabolic communicationNeurovascular unitRedox balanceTight junction

Identifiers

PMID32502899
PMCPMC7267730
OpenAlexW3028149388

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.