Evidence map›Paper›PMID 24113184›Full record

ArticleCell death & disease2013

HIV gp120- and methamphetamine-mediated oxidative stress induces astrocyte apoptosis via cytochrome P450 2E1.

A Shah, S Kumar, S D Simon, D P Singh, A Kumar

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 2 pooled it
5.5field-weighted citation impact, top 5% 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

74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.Redox report : communications in free radical research · 2026
    Article
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  9. Cannabidiol alleviates methamphetamine addictionActa pharmaceutica Sinica. B · 2025
    Article
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14 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

5 authors at 2 institutions in 1 country.

A ShahDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA.
S Kumar
S D Simon
D P Singh
A Kumar
University of Missouri–Kansas City · USUniversity of Nebraska Medical Center · US

Funding

Methamphetamine and AIDS in a Non-Human Primate ModelR01DA025011 · NIDA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KUMAR, ANIL · 2008 to 2014
$1.8M
Alcohol Abuse and HIV-mediated NeurotoxicityR01AA020806 · NIAAA · UNIVERSITY OF MISSOURI KANSAS CITY · PI WANG, JIANPING · 2012 to 2016
$1.7M
HIV, Drug Abuse and NeurotoxicityR01DA025528 · NIDA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KUMAR, ANIL · 2009 to 2013
$1.4M
NIAAA NIH HHS AA020806NIAAA NIH HHS R01 AA020806NIDA NIH HHS DA025011NIDA NIH HHS DA025528NIDA NIH HHS R01 DA025011NIDA NIH HHS R01 DA025528
6 · The paper itself

Abstract

HIV-1 glycoprotein 120 (gp120) is known to cause neurotoxicity via several mechanisms including production of proinflammatory cytokines/chemokines and oxidative stress. Likewise, drug abuse is thought to have a direct impact on the pathology of HIV-associated neuroinflammation through the induction of proinflammatory cytokines/chemokines and oxidative stress. In the present study, we demonstrate that gp120 and methamphetamine (MA) causes apoptotic cell death by inducing oxidative stress through the cytochrome P450 (CYP) and NADPH oxidase (NOX) pathways. The results showed that both MA and gp120 induced reactive oxygen species (ROS) production in concentration- and time-dependent manners. The combination of gp120 and MA also induced CYP2E1 expression at both mRNA (1.7±0.2- and 2.8±0.3-fold in SVGA and primary astrocytes, respectively) and protein (1.3±0.1-fold in SVGA and 1.4±0.03-fold in primary astrocytes) levels, suggesting the involvement of CYP2E1 in ROS production. This was further confirmed by using a selective inhibitor of CYP2E1, diallylsulfide (DAS), and CYP2E1 knockdown using siRNA, which significantly reduced ROS production (30-60%). As the CYP pathway is known to be coupled with the NOX pathway, including Fenton-Weiss-Haber (FWH) reaction, we examined whether the NOX pathway is also involved in ROS production induced by either gp120 or MA. Our results showed that selective inhibitors of NOX, diphenyleneiodonium (DPI), and FWH reaction, deferoxamine (DFO), also significantly reduced ROS production. These findings were further confirmed using specific siRNAs against NOX2 and NOX4 (NADPH oxidase family). We then showed that gp120 and MA both induced apoptosis (caspase-3 activity and DNA lesion using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) assay) and cell death. Furthermore, we showed that DAS, DPI, and DFO completely abolished apoptosis and cell death, suggesting the involvement of CYP and NOX pathways in ROS-mediated apoptotic cell death. In conclusion, this is the first report on the involvement of CYP and NOX pathways in gp120/MA-induced oxidative stress and apoptotic cell death in astrocytes, which has clinical implications in neurodegenerative diseases, including neuroAIDS.

Indexed as

ApoptosisAstrocytesCaspase 3Chelating AgentsCytochrome P-450 CYP2E1Enzyme ActivationFerritinsHIV Envelope Protein gp120HumansMethamphetamineModels, BiologicalNADPH OxidasesOxidative StressReactive Oxygen SpeciesTime FactorsCaspase 3Chelating AgentsCytochrome P-450 CYP2E1FerritinsHIV Envelope Protein gp120MethamphetamineNADPH OxidasesReactive Oxygen Species

Identifiers

PMID24113184
PMCPMC3824683
OpenAlexW2064342286

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.