Evidence map›Paper›PMID 20133634›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced neuroprotection against global cerebral ischemia.

R Anne Stetler, Yanqin Gao, R Suzanne Zukin, Peter S Vosler, Lili Zhang, Feng Zhang, Guodong Cao, Michael V L Bennett, Jun Chen

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
  2. Piperine alleviates retinal ischemic injury by mediating the APE1 signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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

9 authors at 4 institutions in 2 countries.

R Anne StetlerCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Yanqin Gao
R Suzanne Zukin
Peter S Vosler
Lili Zhang
Feng Zhang
Guodong Cao
Michael V L Bennett
Jun Chen
Fudan University · CNUniversity of Pittsburgh · USAlbert Einstein College of Medicine · USYeshiva University · US

Funding

REST-Activated Program of Gene Expression in IschemiaR01NS046742 · NINDS · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI ZUKIN, R. SUZANNE · 2004 to 2019
$6.1M
INDUCIBLE DNA REPAIR IN CEREBRAL ISCHEMIAR01NS036736 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BENNETT, MICHAEL V L, GRAHAM, STEVEN H · 1997 to 2021
$5.4M
Neuroprotection in Models of Cerebral IschemiaR01NS045048 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2003 to 2015
$3.1M
Programmed Cell Death Induced by Cerebral IschemiaR01NS043802 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2002 to 2006
$1.4M
NINDS NIH HHS NS36736NINDS NIH HHS NS43802NINDS NIH HHS NS45048NINDS NIH HHS NS46742NINDS NIH HHS R01 NS036736NINDS NIH HHS R01 NS043802NINDS NIH HHS R01 NS045048NINDS NIH HHS R01 NS046742
6 · The paper itself

Abstract

Inducible DNA repair via the base-excision repair pathway is an important prosurvival mechanism activated in response to oxidative DNA damage. Elevated levels of the essential base-excision repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 correlate closely with neuronal survival against ischemic insults, depending on the CNS region, protective treatments, and degree of insult. However, the precise mechanisms by which this multifunctional protein affords protection and is activated by upstream signaling pathways in postischemic neurons are not well delineated. Here we show that intracerebral administration of pituitary adenylate cyclase-activating polypeptide (PACAP), an endogenously occurring small neuropeptide, induces expression of APE1 in hippocampal neurons. Induction of APE1 expression requires PKA- and p38-dependent phosphorylation of cAMP response-element binding and activating transcription factor 2, which leads to transactivation of the APE1 promoter. We further show that PACAP markedly reduces oxidative DNA stress and hippocampal CA1 neuronal death following transient global ischemia. These effects occurred, at least in part, via enhanced APE1 expression. Furthermore, the DNA repair function of APE1 was required for PACAP-mediated neuroprotection. Thus, induction of DNA repair enzymes may be a unique strategy for neuroprotection against hippocampal injury.

Indexed as

Activating Transcription Factor 2Analysis of VarianceAnimalsApoptosisBrain IschemiaChromatin ImmunoprecipitationCyclic AMP Response Element-Binding ProteinDNA-(Apurinic or Apyrimidinic Site) LyaseDNA RepairElectrophoretic Mobility Shift AssayGene Expression RegulationHippocampusHumansLuciferasesOxidative StressPhosphorylationActivating Transcription Factor 2APEX1 protein, humanCyclic AMP Response Element-Binding ProteinDNA-(Apurinic or Apyrimidinic Site) LyaseLuciferasesPituitary Adenylate Cyclase-Activating Polypeptide

Identifiers

PMID20133634
PMCPMC2840276
OpenAlexW2078900564

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.