Evidence map›Paper›PMID 34800614›Full record

ArticleToxicology letters2022

Manganese phosphorylates Yin Yang 1 at serine residues to repress EAAT2 in human H4 astrocytes.

Asha Rizor, Edward Pajarillo, Deok-Soo Son, Michael Aschner, Eunsook Lee

Open access · greenAbstract read
In one paragraph

Article in Toxicology letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 30% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. [Mechanism of Bushen Yijing Formula improving cognitive function in AlzheimerZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026
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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

5 authors at 4 institutions in 2 countries.

Asha RizorDepartment of Pharmaceutical Sciences, College of Pharmacy, Florida A&M University, Tallahassee, FL, 32301, USA.
Edward PajarilloDepartment of Pharmaceutical Sciences, College of Pharmacy, Florida A&M University, Tallahassee, FL, 32301, USA.
Deok-Soo SonDepartment of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN, 37208, USA.
Michael AschnerDepartment of Molecular Pharmacology, Albert Einstein College of Medicine Bronx, New York, NY, 10461, USA; Sechenov First Moscow State Medical University, Moscow, Russia.
Eunsook LeeDepartment of Pharmaceutical Sciences, College of Pharmacy, Florida A&M University, Tallahassee, FL, 32301, USA. Electronic address: eunsook.lee@famu.edu.
Florida Agricultural and Mechanical University · USAlbert Einstein College of Medicine · USFlorida A&M University - Florida State University College of Engineering · USMeharry Medical College · US

Funding

Research Project-3: Effectiveness of an eHealth intervention for uptake of cervical cancer screening in Hispanic womenU54MD007582 · NIMHD · FLORIDA AGRICULTURAL AND MECHANICAL UNIV · PI KARAM F.A. SOLIMAN · 2019 to 2026
$28.1M
Mechanisms of Manganese NeurotoxicityR01ES010563 · NIEHS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Michael Aschner, Aaron B Bowman · 2001 to 2026
$11.9M
Mechanisms of Methylmercury Induced Neuron ToxicityR01ES007331 · NIEHS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Michael Aschner, Aaron B Bowman · 1996 to 2026
$10.6M
Mechanisms associated with neuroprotection from Mn-induced neurotoxicity.R01ES031282 · NIEHS · FLORIDA AGRICULTURAL AND MECHANICAL UNIV · PI LEE, EUNSOOK YU · 2020 to 2025
$2.4M
Genetic Modulation of MeHg-Induced Oxidative Stress in the Developing BrainR01ES020852 · NIEHS · VANDERBILT UNIVERSITY · PI ASCHNER, MICHAEL · 2012 to 2016
$1.8M
Mechanism of manganese-induced impairment of astrocytic glutamate transportersR01ES024756 · NIEHS · MEHARRY MEDICAL COLLEGE · PI LEE, EUN SOOK YU · 2015 to 2019
$1.8M
Roles of proinflammatory chemokines linking obesity and breast cancerSC1CA200519 · NCI · MEHARRY MEDICAL COLLEGE · PI SON, DEOK-SOO · 2015 to 2018
$1.5M
NCI NIH HHS SC1 CA200519NIEHS NIH HHS R01 ES007331NIEHS NIH HHS R01 ES010563NIEHS NIH HHS R01 ES020852NIEHS NIH HHS R01 ES024756NIEHS NIH HHS R01 ES031282NIMHD NIH HHS U54 MD007582
6 · The paper itself

Abstract

Impairment of the astrocytic glutamate transporter excitatory amino acid transporter 2 (EAAT2) is associated with neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and manganism, a neurological disorder caused by overexposure to manganese (Mn) which shares the features of sporadic PD. Mechanisms of Mn-induced neurotoxicity include dysregulation of EAAT2 following activation of the transcription factor Yin Yang 1 (YY1) by transcriptional upregulation, but the posttranslational mechanisms by which YY1 is activated to repress EAAT2 remain to be elucidated. In the present study, we tested if Mn activates YY1 through posttranslational phosphorylation in cultured H4 human astrocytes, leading to EAAT2 repression. The results demonstrate that Mn exposure induced phosphorylation of YY1 at serine residues via kinases Aurora B kinase (AurkB) and Casein kinase II (CK2), leading to YY1 nuclear translocation, YY1/HDAC interactions, binding to the EAAT2 promoter, and consequent decreases in EAAT2 promoter activity and mRNA/protein levels. Although further studies are warranted to fully elucidate the mechanisms of Mn-induced YY1 phosphorylation and resultant EAAT2 impairment, our findings indicate that serine phosphorylation of YY1 via AurkB and CK2 is critical, at least in part, to its activation and transcriptional repression of EAAT2.

Indexed as

Amino Acid SequenceAstrocytesAurora Kinase BCell LineCheckpoint Kinase 2Excitatory Amino Acid Transporter 2Gene Expression RegulationHumansManganesePhosphorylationSerineYY1 Transcription FactorAURKB protein, humanAurora Kinase BCheckpoint Kinase 2CHEK2 protein, humanExcitatory Amino Acid Transporter 2ManganeseSerineSLC1A2 protein, humanYY1 Transcription FactorAurkBCK2EAAT2ManganeseYY1

Identifiers

PMID34800614
PMCPMC8713424
OpenAlexW3214337197

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.