Evidence map›Paper›PMID 33567754›Full record

ArticleInternational journal of molecular sciences2021

Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo.

Sebastian Granitzer, Raimund Widhalm, Martin Forsthuber, Isabella Ellinger, Gernot Desoye, Markus Hengstschläger, Harald Zeisler, Hans Salzer, Claudia Gundacker

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

12 citing papers in PubMed, 23 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 4 institutions in 1 country.

Sebastian GranitzerKarl-Landsteiner Private University for Health Sciences, A-3500 Krems, Austria.
Raimund WidhalmKarl-Landsteiner Private University for Health Sciences, A-3500 Krems, Austria.
Martin ForsthuberInstitute of Medical Genetics, Medical University of Vienna, A-1090 Vienna, Austria.
Isabella EllingerDepartment of Pathophysiology and Allergy Research, Medical University of Vienna, A-1090 Vienna, Austria.ORCID 0000-0001-6335-076X
Gernot DesoyeDepartment of Obstetrics and Gynecology, Medical University of Graz, A-8036 Graz, Austria.ORCID 0000-0002-5715-3230
Markus HengstschlägerInstitute of Medical Genetics, Medical University of Vienna, A-1090 Vienna, Austria.
Harald ZeislerDepartment of Obstetrics and Gynecology, Medical University Vienna, A-1090 Vienna, Austria.
Hans SalzerClinical Department of Pediatrics and Adolescent Medicine, University Hospital Tulln, A-3430 Tulln, Austria.
Claudia GundackerInstitute of Medical Genetics, Medical University of Vienna, A-1090 Vienna, Austria.ORCID 0000-0003-4093-3780
Medical University of Vienna · ATKarl Landsteiner University of Health Sciences · ATMedical University of Graz · ATUniversitätsklinikum Tulln · AT

Funding

NÖ Forschungs- und Bildungsges.m.b.H. LS15-014
6 · The paper itself

Abstract

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

Indexed as

ApoptosisCells, CulturedCell SurvivalFemaleGlutathioneHumansLarge Neutral Amino Acid-Transporter 1Methylmercury CompoundsOxidative StressPlacentaPregnancyProtective AgentsGlutathioneLarge Neutral Amino Acid-Transporter 1Methylmercury CompoundsProtective AgentsSLC7A5 protein, humanGSHHTR-8/SVneoLAT1MeHgmercuryoxidative stressplacenta

Identifiers

PMID33567754
PMCPMC7915079
OpenAlexW3128663594

What OpenQuestion holds

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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.