Evidence map›Paper›PMID 21303347›Full record

ArticleThe Biochemical journal2011

Neutral sphingomyelinase 2 (nSMase2) is the primary neutral sphingomyelinase isoform activated by tumour necrosis factor-α in MCF-7 cells.

Christopher J Clarke, Emily A Cloessner, Patrick L Roddy, Yusuf A Hannun

Abstract read
In one paragraph

Article in The Biochemical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025
    Review
  3. Article
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  6. Article
  7. Review
  8. Article
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  10. CaNature communications · 2022
    Article
  11. Neutral sphingomyelinase-2 and cardiometabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2021
    Review
  12. Review
  13. Article
  14. Article
  15. Review
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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

4 authors at 1 institution in 1 country.

Christopher J ClarkeDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Emily A Cloessner
Patrick L Roddy
Yusuf A Hannun
Medical University of South Carolina · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
Sphingomyelin Turnover and Cellular RegulationR37GM043825 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2007 to 2015
$3.7M
SPHINGOMYELIN TURNOVER AND CELLULAR REGULATIONR01GM043825 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HANNUN, YUSUF AWNI · 1991 to 2006
$2.2M
NCI NIH HHS P30 CA138313NCRR NIH HHS C06 RR01882NIGMS NIH HHS GM43825NIGMS NIH HHS R01 GM043825NIGMS NIH HHS R37 GM043825
6 · The paper itself

Abstract

Activation of N-SMase (neutral sphingomyelinase) is an established part of the response of cytokines such as TNF (tumour necrosis factor)-α. However, it remains unclear which of the currently cloned N-SMase isoforms (nSMase1, nSMase2 and nSMase3) are responsible for this activity. In MCF-7 cells, we found that TNF-α induces late, but not early, increases in N-SMase activity, and that nSMase2 is the primary isoform activated, most likely through post-transcriptional mechanisms. Surprisingly, overexpression of tagged or untagged nSMase3 in multiple cell lines had no significant effect on in vitro N-SMase activity. Moreover, only overexpression of nSMase2, but not nSMase1 or nSMase3, had significant effects on cellular sphingolipid levels, increasing ceramide and decreasing sphingomyelin. Additionally, only siRNA (small interfering RNA) knockdown of nSMase1 significantly decreased basal in vitro N-SMase activity of MCF-7 cells, whereas nSMase2 but not nSMase3 siRNA inhibited TNF-α-induced activity. Taken together, these results identify nSMase2 as the major TNF-α-responsive N-SMase in MCF-7 cells. Moreover, the results suggest that nSMase3 may not possess in vitro N-SMase activity and does not affect cellular sphingolipid levels in the cell lines evaluated. On the other hand, nSMase1 contributes to in vitro N-SMase activity, but does not affect cellular sphingolipids much.

Indexed as

Breast NeoplasmsCarcinomaCell Line, TumorCells, CulturedEnzyme ActivationFemaleGene Expression Regulation, EnzymologicGene Knockdown TechniquesHumansIsoenzymesRNA, Small InterferingSphingolipidsSphingomyelin PhosphodiesteraseTransfectionTumor Necrosis Factor-alphaUp-RegulationIsoenzymesneutral sphingomyelinase 3, humanRNA, Small InterferingSMPD3 protein, humanSphingolipidsSphingomyelin PhosphodiesteraseTumor Necrosis Factor-alpha

Identifiers

PMID21303347
PMCPMC3715995
OpenAlexW2102299141

What OpenQuestion holds

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LicenceTDM
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.