Evidence map›Paper›PMID 26429731›Full record

ArticleNeurotoxicity research2016

Double-Edged Roles of Nitric Oxide Signaling on APP Processing and Amyloid-β Production In Vitro: Preliminary Evidence from Sodium Nitroprusside.

Zheng-Xu Cai, Hui-Shu Guo, Che Wang, Min Wei, Cheng Cheng, Zhao-Fei Yang, Yin-Wang Chen, Wei-Dong Le, Song Li

Abstract read
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In one paragraph

Article in Neurotoxicity research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017
    Article
  5. Article
  6. 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 3 institutions in 1 country.

Zheng-Xu CaiDepartment of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
Hui-Shu GuoLaboratory Center, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
Che WangDepartment of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, 116029, China.
Min WeiCenter for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China.
Cheng ChengCenter for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China.
Zhao-Fei YangCenter for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China.
Yin-Wang ChenDepartment of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, 116029, China.
Wei-Dong LeCenter for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China. wdle@sibs.ac.cn.
Song LiCenter for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China. lisong_spu2005@yahoo.com.
Dalian Medical University · CNFirst Affiliated Hospital of Dalian Medical University · CNLiaoning Normal University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is thought to be caused in part by the age-related accumulation of amyloid-β (Aβ) in the brain. Recent findings have revealed that nitric oxide (NO) modulates the processing of amyloid-β precursor protein (APP) and alters Aβ production; however, the previously presented data are contradictory and the underlying molecular mechanisms are still incomplete. Here, using human SH-SY5Y neuroblastoma cells stably transfected with wild-type APPwt695, we found that NO, derived from NO donor sodium nitroprusside (SNP), bi-directionally modulates APP processing in vitro. The data from ELISA and Western blot (WB) tests indicated that SNP at lower concentrations (0.01 and 0.1 μM) inhibits BACE1 expression, thus consequently suppresses APP β-cleavage and decreases Aβ production. In contrast, SNP at higher concentrations (10 and 20 μM) biases the APP processing toward the amyloidogenic pathway as evidenced by an increased BACE1 but a decreased ADAM10 expression, together with an elevated Aβ secretion. This bi-directional modulating activity of SNP on APP processing was completely blocked by specific NO scavenger c-PTIO, indicating NO-dependent mechanisms. Moreover, the anti-amyloidogenic activity of SNP is sGC/cGMP/PKG-dependent as evidenced by its reversal by sGC/PKG inhibitions, whereas the amyloidogenic activity of SNP is peroxynitrite-related and can be reversed by peroxynitrite scavenger uric acid. In summary, these present findings predict a double-edged role of NO in APP processing in vitro. Low (physiological) levels of NO inhibit the amyloidogenic processing of APP, whereas extra-high (pathological) concentrations of NO favor the amyloidogenic pathway of APP processing. This preliminary study may provide further evidence to clarify the molecular roles of NO and NO-related signaling in AD and supply potential molecular targets for AD treatment.

Indexed as

ADAM10 ProteinADAM ProteinsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesCarbazolesCell Line, TumorCyclic GMPCyclic N-OxidesDose-Response Relationship, DrugEnzyme InhibitorsGene Expression RegulationHumansImidazolesMembrane Proteins2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxideADAM10 ProteinADAM10 protein, humanADAM ProteinsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humanCarbazolesCyclic GMPCyclic N-OxidesEnzyme InhibitorsImidazolesKT 5823Membrane ProteinsNitric OxideNitric Oxide DonorsNitroprussidePeroxynitrous AcidSuperoxidesAmyloid-βAmyloid-β precursor proteinNitric oxidePeroxynitritesGC/cGMP/PKG signaling pathwaySodium nitroprusside

Identifiers

PMID26429731
OpenAlexW2173834847

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.