Evidence map›Paper›PMID 32430797›Full record

ArticleTranslational stroke research2021

TRPM7 Mediates Neuronal Cell Death Upstream of Calcium/Calmodulin-Dependent Protein Kinase II and Calcineurin Mechanism in Neonatal Hypoxic-Ischemic Brain Injury.

Ekaterina Turlova, Raymond Wong, Baofeng Xu, Feiya Li, Lida Du, Steven Habbous, F David Horgen, Andrea Fleig, Zhong-Ping Feng, Hong-Shuo Sun

Abstract read
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In one paragraph

Article in Translational stroke research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
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  9. Article
  10. Unlocking TRPM7 interactions: A database-driven quest.Computational and structural biotechnology journal · 2025
    Review
  11. Review
  12. Review
  13. Role of TRP Channels in Metabolism-Related Diseases.International journal of molecular sciences · 2024
    Review
  14. Article
  15. Article
  16. Article
  17. Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Article
  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

10 authors at 4 institutions in 2 countries.

Ekaterina Turlova *Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Raymond Wong *Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Baofeng XuDepartment of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Feiya LiDepartment of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Lida DuDepartment of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Steven HabbousDepartment of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
F David HorgenDepartment of Natural Sciences, Hawaii Pacific University, Kaneohe, HI, 96744, USA.
Andrea FleigCenter for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96720, USA.
Zhong-Ping FengDepartment of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. zp.feng@utoronto.ca.
Hong-Shuo SunDepartment of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. hss.sun@utoronto.ca.
University of Toronto · CACanada Research Chairs · CAHawaii Pacific University · USUniversity of Hawaiʻi at Mānoa · US

Funding

Natural Sciences and Engineering Research Council of Canada RGPIN-2014-06471Natural Sciences and Engineering Research Council of Canada RGPIN-2016-04574
6 · The paper itself

Abstract

Transient receptor potential melastatin 7 (TRPM7), a calcium-permeable, ubiquitously expressed ion channel, is critical for axonal development, and mediates hypoxic and ischemic neuronal cell death in vitro and in vivo. However, the downstream mechanisms underlying the TRPM7-mediated processes in physiology and pathophysiology remain unclear. In this study, we employed a mouse model of hypoxic-ischemic brain cell death which mimics the pathophysiology of hypoxic-ischemic encephalopathy (HIE). HIE is a major public health issue and an important cause of neonatal deaths worldwide; however, the available treatments for HIE remain limited. Its survivors face life-long neurological challenges including mental retardation, cerebral palsy, epilepsy and seizure disorders, motor impairments, and visual and auditory impairments. Through a proteomic analysis, we identified calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphatase calcineurin as potential mediators of cell death downstream from TRPM7 activation. Further analysis revealed that TRPM7 mediates cell death through CaMKII, calmodulin, calcineurin, p38, and cofilin cascade. In vivo, we found a significant reduction of brain injury and improvement of short- and long-term functional outcomes after HI after administration of specific TRPM7 blocker waixenicin A. Our data demonstrate a molecular mechanism of TRPM7-mediated cell death and identifies TRPM7 as a promising therapeutic and drug development target for HIE.

Indexed as

AcetatesAnimalsAnimals, NewbornAvoidance LearningCalcineurinCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell DeathCells, CulturedDiterpenesFemaleHEK293 CellsHumansHypoxia-Ischemia, BrainMaleMiceNeuronsAcetatesCalcineurinCalcium-Calmodulin-Dependent Protein Kinase Type 2DiterpenesTrpm7 protein, mouseTRPM Cation Channelswaixenicin ACalcineurinCalcium/calmodulin-dependent protein kinase IICofilinHypoxic-ischemic brain injuryIon channelNeuroprotectionTRPM7Waixenicin A

Identifiers

PMID32430797
OpenAlexW3028014057

What OpenQuestion holds

Textmetadata
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.