Evidence map›Paper›PMID 33054131›Full record

ArticleHaematologica2021

Protein-L-isoaspartate O-methyltransferase is required for

Angelo D'Alessandro, Ariel Hay, Monika Dzieciatkowska, Benjamin C Brown, Evan J Morrison, Kirk C Hansen, James C Zimring

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.3field-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

30 citing papers in PubMed, 32 citations in OpenAlex.

  1. Trial
  2. Article
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  5. High-Throughput Metabolomics in Transfusion Medicine.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  6. Article
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  8. Repair of Isoaspartyl Residues by PCMT1 and Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2025
    Article
  9. Article
  10. Review
  11. It's in your blood: The impact of age, sex, genetic factors and exposures on stored red blood cell metabolism.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2024
    Review
  12. Article
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  19. Red Blood Cell Omics and Machine Learning in Transfusion Medicine: Singularity Is Near.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2023
    Review
  20. 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 at 3 institutions in 1 country.

Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO. angelo.dalessandro@ucdenver.edu.
Ariel HayUniversity of Virginia, Charlotesville, VA.
Monika DzieciatkowskaDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO.
Benjamin C BrownDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO.
Evan J MorrisonDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO.
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO.
James C ZimringUniversity of Virginia, Charlotesville, VA. jcz2k@virginia.edu.
University of Colorado Denver · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Virginia · US

Funding

Resuscitation Strategies for Achieving Thrombo-inflammatory HomeostasisRM1GM131968 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI COHEN, MITCHELL, D'ALESSANDRO, ANGELO · 2019 to 2023
$11.3M
The Impact of Oxidative Stress on Erythocyte BiologyR01HL148151 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ALESSANDRO, ANGELO, KARAFIN, MATTHEW S · 2019 to 2022
$8.9M
The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
Predoctoral Training Program in Molecular and Cellular Biology (Supplement: Mentoring in the Research Environment)T32GM136444 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MICHAEL A MCMURRAY, Rytis Prekeris · 2020 to 2026
$3.7M
Interactions between the ADORA2b/Sphk1axis and the AE1-Hb switch in red blood cell aging in vivo and in vitroR01HL149714 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI D'ALESSANDRO, ANGELO · 2020 to 2023
$2.6M
MIRAGES: Metabolic Investigation of Red blood cells as a function of Aging, Genetics, Environment, and StorageR21HL150032 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI D'ALESSANDRO, ANGELO · 2020 to 2021
$414k
NHLBI NIH HHS R01 HL146442NHLBI NIH HHS R01 HL148151NHLBI NIH HHS R01 HL149714NHLBI NIH HHS R21 HL150032NIGMS NIH HHS RM1 GM131968NIGMS NIH HHS T32 GM136444
6 · The paper itself

Abstract

Red blood cells have the special challenge of a large amount of reactive oxygen species (from their substantial iron load and Fenton reactions) combined with the inability to synthesize new gene products. Considerable progress has been made in elucidating the multiple pathways by which red blood cells neutralize reactive oxygen species via NADPH driven redox reactions. However, far less is known about how red blood cells repair the inevitable damage that does occur when reactive oxygen species break through anti-oxidant defenses. When structural and functional proteins become oxidized, the only remedy available to red blood cells is direct repair of the damaged molecules, as red blood cells cannot synthesize new proteins. Amongst the most common amino acid targets of oxidative damage is the conversion of asparagine and aspartate side chains into a succinimidyl group through deamidation or dehydration, respectively. Red blood cells express an L-Isoaspartyl methyltransferase (PIMT, gene name PCMT1) that can convert succinimidyl groups back to an aspartate. Herein, we report that deletion of PCMT1 significantly alters red blood cell metabolism in a healthy state, but does not impair the circulatory lifespan of red blood cells. Through a combination of genetic ablation, bone marrow transplantation and oxidant stimulation with phenylhydrazine in vivo or blood storage ex vivo, we use omics approaches to show that, when animals are exposed to oxidative stress, red blood cells from PCMT1 knockout undergo significant metabolic reprogramming and increased hemolysis. This is the first report of an essential role of PCMT1 for normal RBC circulation during oxidative stress.

Indexed as

Isoaspartic AcidProtein D-Aspartate-L-Isoaspartate MethyltransferaseAnimalsErythrocytesOxidative StressReactive Oxygen SpeciesIsoaspartic AcidProtein D-Aspartate-L-Isoaspartate MethyltransferaseReactive Oxygen Species

Identifiers

PMID33054131
PMCPMC8485689
OpenAlexW3086037264

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.