Evidence map›Paper›PMID 24928515›Full record

ArticleThe Journal of biological chemistry2014

Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse cortical neurons.

Rui Sheng, Tong-Tong Zhang, Valeria D Felice, Tao Qin, Zheng-Hong Qin, Charles D Smith, Ellen Sapp, Marian Difiglia, Christian Waeber

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Guideline
  2. Review
  3. TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
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  8. Role of NaJournal of molecular medicine (Berlin, Germany) · 2022
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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

9 authors at 4 institutions in 3 countries.

Rui Sheng
Tong-Tong Zhang
Valeria D Felice
Tao Qin
Zheng-Hong Qin
Charles D Smith
Ellen Sapp
Marian Difiglia
Christian Waeber
Soochow University · CNMassachusetts General Hospital · USUniversity College Cork · IEApogee Biotechnology (United States) · US

Funding

Targeting ROCK for Neurogliovascular Plasticity & Remodeling After StrokeP01NS055104 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H. · 2007 to 2018
$13.3M
Interdepartmental Neuroscience CenterP30NS045776 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, TANNOUS, BAKHOS A · 2003 to 2018
$11.1M
Neuron-Dervied S1P and Endothelial Function in StrokeR01NS049263 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI WAEBER, CHRISTIAN · 2006 to 2010
$1.9M
NINDS NIH HHS NS049263NINDS NIH HHS NS055104NINDS NIH HHS P01 NS055104NINDS NIH HHS P30 NS045776NINDS NIH HHS P30NS045776NINDS NIH HHS R01 NS049263
6 · The paper itself

Abstract

Sphingosine kinase 2 (SPK2) and autophagy are both involved in brain preconditioning, but whether preconditioning-induced SPK2 up-regulation and autophagy activation are linked mechanistically remains to be elucidated. In this study, we used in vitro and in vivo models to explore the role of SPK2-mediated autophagy in isoflurane and hypoxic preconditioning. In primary mouse cortical neurons, both isoflurane and hypoxic preconditioning induced autophagy. Isoflurane and hypoxic preconditioning protected against subsequent oxygen glucose deprivation or glutamate injury, whereas pretreatment with autophagy inhibitors (3-methyladenine or KU55933) abolished preconditioning-induced tolerance. Pretreatment with SPK2 inhibitors (ABC294640 and SKI-II) or SPK2 knockdown prevented preconditioning-induced autophagy. Isoflurane also induced autophagy in mouse in vivo as shown by Western blots for LC3 and p62, LC3 immunostaining, and electron microscopy. Isoflurane-induced autophagy in mice lacking the SPK1 isoform (SPK1(-/-)), but not in SPK2(-/-)mice. Sphingosine 1-phosphate and the sphingosine 1-phosphate receptor agonist FTY720 did not protect against oxygen glucose deprivation in cultured neurons and did not alter the expression of LC3 and p62, suggesting that SPK2-mediated autophagy and protections are not S1P-dependent. Beclin 1 knockdown abolished preconditioning-induced autophagy, and SPK2 inhibitors abolished isoflurane-induced disruption of the Beclin 1/Bcl-2 association. These results strongly indicate that autophagy is involved in isoflurane preconditioning both in vivo and in vitro and that SPK2 contributes to preconditioning-induced autophagy, possibly by disrupting the Beclin 1/Bcl-2 interaction.

Indexed as

AutophagyIschemic PreconditioningAdamantaneAnesthetics, InhalationAnimalsApoptosis Regulatory ProteinsBeclin-1Cells, CulturedCerebral CortexEnzyme InhibitorsIsofluraneLactosylceramidesMiceMice, KnockoutMorpholinesNeurons2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amideAdamantaneAnesthetics, InhalationApoptosis Regulatory ProteinsBeclin-1Becn1 protein, mouseEnzyme InhibitorsGtf2h1 protein, mouseIsofluraneLactosylceramideslactotriaosylceramideMorpholinesPhosphotransferases (Alcohol Group Acceptor)Proto-Oncogene Proteins c-bcl-2PyridinesPyronesSphingosine KinaseTranscription FactorsTranscription Factor TFIIH

Identifiers

PMID24928515
PMCPMC4110292
OpenAlexW2027540537

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.