Evidence map›Paper›PMID 26243186›Full record

ArticleMolecular neurobiology2016

Cocaine-Mediated Autophagy in Astrocytes Involves Sigma 1 Receptor, PI3K, mTOR, Atg5/7, Beclin-1 and Induces Type II Programed Cell Death.

Lu Cao, Mary P Walker, Naveen K Vaidya, Mingui Fu, Santosh Kumar, Anil Kumar

Abstract read
In one paragraph

Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
4.4field-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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Lu CaoDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA.
Mary P WalkerDepartment of Oral and Craniofacial Sciences, School of Dentistry Center of Excellence in Musculoskeletal and Dental Tissues, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
Naveen K VaidyaDepartment of Mathematics and Statistics, University of Missouri, Kansas City, MO, 64110, USA.
Mingui FuDepartment of Basic Medical Science, School of Medicine, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
Santosh KumarDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Anil KumarDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA. kumaran@umkc.edu.ORCID 0000-0003-2110-7731
University of Missouri–Kansas City · USUniversity of Tennessee Health Science 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
HIV, Drug Abuse and NeurotoxicityR01DA025528 · NIDA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KUMAR, ANIL · 2009 to 2013
$1.4M
Zeiss LSM 710 Confocal Microscopy System for Imaging of Mineralized TissuesS10RR027668 · NCRR · UNIVERSITY OF MISSOURI KANSAS CITY · PI DALLAS, SARAH L · 2011 to 2011
$446k
NCRR NIH HHS S10 RR027668NIDA NIH HHS R01 DA025011NIDA NIH HHS R01 DA025528
6 · The paper itself

Abstract

Cocaine, a commonly used drug of abuse, has been shown to cause neuropathological dysfunction and damage in the human brain. However, the role of autophagy in this process is not defined. Autophagy, generally protective in nature, can also be destructive leading to autophagic cell death. This study was designed to investigate whether cocaine induces autophagy in the cells of CNS origin. We employed astrocyte, the most abundant cell in the CNS, to define the effects of cocaine on autophagy. We measured levels of the autophagic marker protein LC3II in SVGA astrocytes after exposure with cocaine. The results showed that cocaine caused an increase in LC3II level in a dose- and time-dependent manner, with the peak observed at 1 mM cocaine after 6-h exposure. This result was also confirmed by detecting LC3II in SVGA astrocytes using confocal microscopy and transmission electron microscopy. Next, we sought to explore the mechanism by which cocaine induces the autophagic response. We found that cocaine-induced autophagy was mediated by sigma 1 receptor, and autophagy signaling proteins p-mTOR, Atg5, Atg7, and p-Bcl-2/Beclin-1 were also involved, and this was confirmed by using selective inhibitors and small interfering RNAs (siRNAs). In addition, we found that chronic treatment with cocaine resulted in cell death, which is caspase-3 independent and can be ameliorated by autophagy inhibitor. Therefore, this study demonstrated that cocaine induces autophagy in astrocytes and is associated with autophagic cell death.

Indexed as

ApoptosisAstrocytesAutophagyAutophagy-Related ProteinsBeclin-1Caspase 3CocaineHumansMicrotubule-Associated ProteinsModels, BiologicalPhosphatidylinositol 3-KinasesReceptors, sigmaSigma-1 ReceptorSignal TransductionTime FactorsTOR Serine-Threonine KinasesAutophagy-Related ProteinsBeclin-1Caspase 3CocaineMAP1LC3A protein, humanMicrotubule-Associated ProteinsPhosphatidylinositol 3-KinasesReceptors, sigmaSigma-1 ReceptorTOR Serine-Threonine KinasesAstrocytesAutophagyCocainemTORsiRNAs

Identifiers

PMID26243186
PMCPMC4744147
OpenAlexW1088785697

What OpenQuestion holds

Textmetadata
LicenceTDM
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.