Evidence map›Paper›PMID 22108004›Full record

ArticleAutophagy2011

Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells.

Lin Zheng, Alexei Terman, Martin Hallbeck, Nodi Dehvari, Richard F Cowburn, Eirikur Benedikz, Katarina Kågedal, Angel Cedazo-Minguez, Jan Marcusson

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. The cellular model for Alzheimer's disease research: PC12 cells.Frontiers in molecular neuroscience · 2022
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Alternative autophagy: mechanisms and roles in different diseases.Cell communication and signaling : CCS · 2022
    Review
  14. Review
  15. Article
  16. NADCell reports · 2021
    Article
  17. Schizandrol A protects against AβNaunyn-Schmiedeberg's archives of pharmacology · 2020
    Article
  18. LL-37-Induced Autophagy Contributed to the Elimination of LiveFrontiers in cellular and infection microbiology · 2020
    Article
  19. Review
  20. Review
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 6 institutions in 5 countries.

Lin ZhengDivision of Geriatric Medicine, Department of Clinical and Experimental Medicine, IKE, Faculty of Health Sciences, Linköping University, Linköping, Sweden. lin.zheng@liu.se
Alexei Terman
Martin Hallbeck
Nodi Dehvari
Richard F Cowburn
Eirikur Benedikz
Katarina Kågedal
Angel Cedazo-Minguez
Jan Marcusson
Karolinska Institutet · SELinköping University · SEAstraZeneca (Sweden) · SEFaculty of Public Health · GBKarolinska University Hospital · SELinköping University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increasing evidence suggests the toxicity of intracellular amyloid β-protein (Aβ) to neurons, as well as the involvement of oxidative stress in Alzheimer disease (AD). Here we show that normobaric hyperoxia (exposure of cells to 40% oxygen for five days), and consequent activation of macroautophagy and accumulation of Aβ within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as Aβ monomers and oligomers, (2) increased reactive oxygen species production, and (3) enhanced apoptosis. Oxidant-induced apoptosis positively correlated with cellular Aβ production, being the highest in cells that were stably transfected with APP Swedish KM670/671NL double mutation. Inhibition of γ-secretase, prior and/or in parallel to hyperoxia, suggested that the increase of lysosomal Aβ resulted mainly from its autophagic uptake, but also from APP processing within autophagic vacuoles. The oxidative stress-mediated effects were prevented by macroautophagy inhibition using 3-methyladenine or ATG5 downregulation. Our results suggest that upregulation of macroautophagy and resulting lysosomal Aβ accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide additional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration.

Indexed as

AdenineAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesApoptosisAutophagyAutophagy-Related Protein 5Cell DifferentiationCell NucleusCell SurvivalDown-RegulationHumansIntracellular SpaceLysosomal-Associated Membrane Protein 2Lysosomal Membrane ProteinsLysosomesMicrotubule-Associated Proteins3-methyladenineAdenineAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesATG5 protein, humanAutophagy-Related Protein 5LAMP2 protein, humanLysosomal-Associated Membrane Protein 2Lysosomal Membrane ProteinsMicrotubule-Associated ProteinsMutant ProteinsOxidantsOxygenReactive Oxygen SpeciesRNA, Small InterferingTretinoin

Identifiers

PMID22108004
PMCPMC3288025
OpenAlexW1981964613

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.