Evidence map›Paper›PMID 41185624›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Secondary Necrosis Following Caspase-Activation can Occur Independently of Gasdermin E.

Shubhangi Gavali, Francesca Maremonti, Wulf Tonnus, Florian Gembardt, Marlena Nastassja Schlecht, Karolin Flade, Anne von Mässenhausen, Stephen W G Tait, Stefan R Bornstein, Andreas Linkermann

Abstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Secondary Necrosis Following Caspase-Activation can Occur Independently of Gasdermin E.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    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.

Shubhangi GavaliDepartment of Medicine V, University Medical Centre Mannheim, University of Heidelberg, 68167, Mannheim, Germany.ORCID https://orcid.org/0000-0003-2876-1453
Francesca MaremontiDepartment of Medicine V, University Medical Centre Mannheim, University of Heidelberg, 68167, Mannheim, Germany.
Wulf TonnusDepartment of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307, Dresden, Germany.
Florian GembardtDepartment of Medicine V, University Medical Centre Mannheim, University of Heidelberg, 68167, Mannheim, Germany.
Marlena Nastassja SchlechtDepartment of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307, Dresden, Germany.
Karolin FladeDepartment of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307, Dresden, Germany.
Anne von MässenhausenInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127, Bonn, Germany.
Stephen W G TaitCancer Research UK Scotland Institute, Glasgow, 461 1BD, UK.ORCID https://orcid.org/0000-0001-7697-132X
Stefan R BornsteinDepartment of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307, Dresden, Germany.
Andreas LinkermannDepartment of Medicine V, University Medical Centre Mannheim, University of Heidelberg, 68167, Mannheim, Germany.ORCID https://orcid.org/0000-0001-6287-9725

Funding

BMBF FERROPathconsortiumDeutsche Forschungsgemeinschaft IRTG 2251Deutsche Forschungsgemeinschaft IRTG 3019Deutsche Forschungsgemeinschaft LI2107/10-1Deutsche Forschungsgemeinschaft SachbeihilfeDeutsche Forschungsgemeinschaft SFB-TRR 127Deutsche Forschungsgemeinschaft SFB-TRR205Deutsche Forschungsgemeinschaft SPP2306Heisenberg-Professorship 324141047
6 · The paper itself

Abstract

Regulated necrosis is a known direct consequence of activation of the necroptosis- and pyroptosis- pathways, but may also result from apoptosis in a process referred to as secondary necrosis. Apoptosis is well understood to be mediated by caspase activation, but the mechanisms that lead to plasma membrane rupture in secondary necrosis remain considerably obscure. Recent data suggested a caspase-mediated cleavage of gasdermin E (GSDME), a member of the gasdermin family. Here, apoptosis induced by diphtheria toxin (DT) is employed as a novel tool to study secondary necrosis. In addition, cisplatin and anti-Fas monoclonal antibody Jo2 are employed to study secondary necrosis in cell culture and in vivo, respectively. Despite prominent, yet epiphenomenal cleavage of GSDME, it is demonstrated that silencing or CRISPR/Cas9-mediated knockout of GSDME does not compromise the kinetics of secondary necrosis induced by DT or cisplatin. During Jo2-induced acute liver toxicity in mice, GSDME expressed in the necrotic liver is detected predominantly in its uncleaved form. In conclusion, the hypothesis of GSDME to be a central mediator of secondary necrosis in these model systems is disproved.

Indexed as

CaspasesNecrosisAnimalsApoptosisGasderminsHumansMiceMice, Inbred C57BLNecroptosisPhosphate-Binding ProteinsPyroptosisCaspasesGasderminsGsdme protein, mousePhosphate-Binding ProteinsB cell lymphoma 2 (BCL2)death receptorimmunotoxinsregulated necrosis

Identifiers

PMID41185624
PMCPMC12697764

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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.