Evidence map›Paper›PMID 25529920›Full record

ArticleJournal of lipid research2015

Lipid-induced NOX2 activation inhibits autophagic flux by impairing lysosomal enzyme activity.

Bharat Jaishy, Quanjiang Zhang, Heaseung S Chung, Christian Riehle, Jamie Soto, Stephen Jenkins, Patrick Abel, L Ashley Cowart, Jennifer E Van Eyk, E Dale Abel

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 123 citations in OpenAlex.

  1. HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.Redox report : communications in free radical research · 2026
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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Bharat JaishyDivision of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Quanjiang ZhangDivision of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Heaseung S ChungDepartment of Biological Chemistry, Johns Hopkins University, Baltimore, MD 21224.
Christian RiehleDivision of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Jamie SotoDivision of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Stephen JenkinsDivision of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112.
Patrick AbelDivision of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112.
L Ashley CowartDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29403.
Jennifer E Van EykDepartment of Biological Chemistry, Johns Hopkins University, Baltimore, MD 21224; Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD 21224; Bayview Proteomics Center, Johns Hopkins University, Baltimore, MD 21224.
E Dale AbelDivision of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242. Electronic address: DRCadmin@uiowa.edu.
University of Utah · USJohns Hopkins University · USUniversity of Iowa · USFraternal Order of Eagles · USMedical University of South Carolina · US

Funding

Translational Research Skills Development CoreU54HL112311 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S, ZIMMERMAN, GUY A. · 2012 to 2016
$12.9M
Sphingolipids in Diabetic CardiomyopathyR01HL117233 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI COWART, LAUREN ASHLEY · 2014 to 2018
$1.9M
Insulin Resistance and Myocardial AutophagyR01HL108379 · NHLBI · UNIVERSITY OF UTAH · PI ABEL, E DALE · 2011 to 2014
$1.5M
NHLBI NIH HHS R01 HL108379NHLBI NIH HHS R01HL108379NHLBI NIH HHS R01 HL117233NHLBI NIH HHS U54 HL112311
6 · The paper itself

Abstract

Autophagy is a catabolic process involved in maintaining energy and organelle homeostasis. The relationship between obesity and the regulation of autophagy is cell type specific. Despite adverse consequences of obesity on cardiac structure and function, the contribution of altered cardiac autophagy in response to fatty acid overload is incompletely understood. Here, we report the suppression of autophagosome clearance and the activation of NADPH oxidase (Nox)2 in both high fat-fed murine hearts and palmitate-treated H9C2 cardiomyocytes (CMs). Defective autophagosome clearance is secondary to superoxide-dependent impairment of lysosomal acidification and enzyme activity in palmitate-treated CMs. Inhibition of Nox2 prevented superoxide overproduction, restored lysosome acidification and enzyme activity, and reduced autophagosome accumulation in palmitate-treated CMs. Palmitate-induced Nox2 activation was dependent on the activation of classical protein kinase Cs (PKCs), specifically PKCβII. These findings reveal a novel mechanism linking lipotoxicity with a PKCβ-Nox2-mediated impairment in pH-dependent lysosomal enzyme activity that diminishes autophagic turnover in CMs.

Indexed as

AnimalsAutophagyCell LineDietary FatsEnzyme ActivationLysosomesMembrane GlycoproteinsMiceMyocytes, CardiacNADPH Oxidase 2NADPH OxidasesPalmitic AcidProtein Kinase C betaRatsSuperoxidesCybb protein, mouseCybb protein, ratDietary FatsMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesPalmitic AcidPrkcb protein, mousePrkcb protein, ratProtein Kinase C betaSuperoxidesautophagycardiomyocytesfatty acidslysosomesNADPH oxidase 2protein kinase Cβ

Identifiers

PMID25529920
PMCPMC4340303
OpenAlexW1972853687

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.