Evidence map›Paper›PMID 22591512›Full record

ArticleASN neuro2012

Role of endolysosomes in HIV-1 Tat-induced neurotoxicity.

Liang Hui, Xuesong Chen, Norman J Haughey, Jonathan D Geiger

Open access · goldAbstract read
In one paragraph

Article in ASN neuro, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
2.3field-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

76 citing papers in PubMed, 88 citations in OpenAlex.

  1. Review
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  9. Review
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  11. Article
  12. Review
  13. HIV-1 gp120-Induced Endolysosome de-Acidification Leads to Efflux of Endolysosome Iron, and Increases in Mitochondrial Iron and Reactive Oxygen Species.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022
    Article
  14. Article
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  16. HIV-1 Tat endocytosis and retention in endolysosomes affects HIV-1 Tat-induced LTR transactivation in astrocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  17. Review
  18. Endolysosome Localization of ERα Is Involved in the Protective Effect of 17α-Estradiol against HIV-1 gp120-Induced Neuronal Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  19. Review
  20. Article

16 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Liang HuiDepartment of Pharmacology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA.
Xuesong Chen
Norman J Haughey
Jonathan D Geiger
University of North Dakota · USJohns Hopkins University · US

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2M
TRPC1, CALCIUM AND PARKINSON'S DISEASEP20RR017699 · NCRR · UNIVERSITY OF NORTH DAKOTA · PI GHRIBI, OTHMAN · 2002 to 2011
$19.7M
HIV Associated CNS Dysfunction with AgingR01AG023471 · NIA · JOHNS HOPKINS UNIVERSITY · PI HAUGHEY, NORMAN J · 2003 to 2007
$1.8M
HIV Mediated Dysfunction of Neural Progenitor CellsR21MH072534 · NIMH · JOHNS HOPKINS UNIVERSITY · PI HAUGHEY, NORMAN J · 2005 to 2006
$421k
Perturbation of amyloid processing in HANDR21AG034849 · NIA · JOHNS HOPKINS UNIVERSITY · PI HAUGHEY, NORMAN J · 2010 to 2011
$377k
NCRR NIH HHS 2P20RR17699NCRR NIH HHS P20 RR017699NIA NIH HHS R01 AG023471NIA NIH HHS R21 AG034849NIMH NIH HHS R21 MH072534
6 · The paper itself

Abstract

Combined anti-retroviral therapeutic drugs effectively increase the lifespan of HIV-1-infected individuals who then have a higher prevalence of HAND (HIV-1 associated neurocognitive disorder). Soluble factors including HIV-1 proteins released from HIV-1-infected cells have been implicated in the pathogenesis of HAND, and particular attention has been paid to the HIV-1 Tat (transactivator of transcription) protein because of its ability to directly excite neurons and cause neuronal cell death. Since HIV-1 Tat enters cells by receptor-mediated endocytosis and since endolysosomes play an important role in neuronal cell life and death, we tested here the hypothesis that HIV-1 Tat neurotoxicity is associated with changes in the endolysosome structure and function and also autophagy. Following the treatment of primary cultured rat hippocampal neurons with HIV-1 Tat or as controls mutant-Tat or PBS, neuronal viability was determined using a triple staining method. Preceding observations of HIV-1 Tat-induced neuronal cell death, we observed statistically significant changes in the structure and membrane integrity of endolysosomes, endolysosome pH and autophagy. As early as 24 h after HIV-1 Tat was applied to neurons, HIV-1 Tat accumulated in endolysosomes, endolysosome morphology was affected and their size increased, endolysosome membrane integrity was disrupted, endolysosome pH increased, specific activities of endolysosome enzymes decreased and autophagy was inhibited, as indicated by the significant changes in three markers for autophagy. In contrast, statistically significant levels of HIV-1 Tat-induced neuronal cell death were observed only after 48 h of HIV-1 Tat treatment. Our findings suggest that endolysosomes are involved in HIV-1 Tat-induced neurotoxicity and may represent a target for therapeutic intervention against HAND.

Indexed as

Analysis of VarianceAnimalsAutophagyCell DeathCell MembraneCells, CulturedEmbryo, MammalianGene Expression RegulationHippocampusHydrogen-Ion ConcentrationLysosomal-Associated Membrane Protein 1LysosomesMicroscopy, ConfocalNeuronsRatstat Gene Products, Human Immunodeficiency Virusearly endosome antigen 1Lysosomal-Associated Membrane Protein 1tat Gene Products, Human Immunodeficiency VirusVesicular Transport Proteins

Identifiers

PMID22591512
PMCPMC3379000
OpenAlexW1982498393

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.