Evidence map›Paper›PMID 26444017›Full record

ArticlePloS one2015

Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion Injury.

Bhavya B Chandrika, Cheng Yang, Yang Ou, Xiaoke Feng, Djamali Muhoza, Alexandrea F Holmes, Sue Theus, Sarika Deshmukh, Randy S Haun, Gur P Kaushal

Abstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

56 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Bhavya B ChandrikaDepartment of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Cheng YangDepartment of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Yang OuDepartment of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Xiaoke FengDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Djamali MuhozaDepartment of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Alexandrea F HolmesCentral Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
Sue TheusCentral Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
Sarika DeshmukhDepartment of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Randy S HaunDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America; Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
Gur P KaushalDepartment of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America; Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.

Funding

Arkansas Center for Clinical and Translational ResearchUL1TR000039 · NCATS · UNIV OF ARKANSAS FOR MED SCIS · PI BECK, CORNELIA MARIE, JAMES, LAURA P · 2012 to 2014
$10.0M
Training Program in the Pathophysiology of Renal DiseaseT32DK061921 · NIDDK · UNIV OF ARKANSAS FOR MED SCIS · PI ARTHUR, JOHN M. · 2006 to 2016
$1.2M
Meprin A Metalloproteinase in Acute Kidney InjuryR01DK081690 · NIDDK · UNIV OF ARKANSAS FOR MED SCIS · PI KAUSHAL, GUR PRASAD · 2010 to 2013
$866k
Role of serine protease KLK7 in pancreatic cancerI01BX000828 · VA · CENTRAL ARKANSAS VETERANS HLTHCARE SYS · PI HAUN, RANDY S. · 2011 to 2014
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BLRD VA I01 BX000444BLRD VA I01 BX000828NCATS NIH HHS UL1 TR000039NCATS NIH HHS UL1TR000039NIDDK NIH HHS R01 DK081690NIDDK NIH HHS R01DK081690NIDDK NIH HHS T32 DK061921NIDDK NIH HHS T32DK061921
6 · The paper itself

Abstract

We examined whether endoplasmic reticulum (ER) stress-induced autophagy provides cytoprotection from renal tubular epithelial cell injury due to oxidants and chemical hypoxia in vitro, as well as from ischemia-reperfusion (IR) injury in vivo. We demonstrate that the ER stress inducer tunicamycin triggers an unfolded protein response, upregulates ER chaperone Grp78, and activates the autophagy pathway in renal tubular epithelial cells in culture. Inhibition of ER stress-induced autophagy accelerated caspase-3 activation and cell death suggesting a pro-survival role of ER stress-induced autophagy. Compared to wild-type cells, autophagy-deficient MEFs subjected to ER stress had enhanced caspase-3 activation and cell death, a finding that further supports the cytoprotective role of ER stress-induced autophagy. Induction of autophagy by ER stress markedly afforded cytoprotection from oxidants H2O2 and tert-Butyl hydroperoxide and from chemical hypoxia induced by antimycin A. In contrast, inhibition of ER stress-induced autophagy or autophagy-deficient cells markedly enhanced cell death in response to oxidant injury and chemical hypoxia. In mouse kidney, similarly to renal epithelial cells in culture, tunicamycin triggered ER stress, markedly upregulated Grp78, and activated autophagy without impairing the autophagic flux. In addition, ER stress-induced autophagy markedly ameliorated renal IR injury as evident from significant improvement in renal function and histology. Inhibition of autophagy by chloroquine markedly increased renal IR injury. These studies highlight beneficial impact of ER stress-induced autophagy in renal ischemia-reperfusion injury both in vitro and in vivo.

Indexed as

Adenosine TriphosphateAnimalsAutophagyCaspasesCell LineCytoprotectionEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressHeat-Shock ProteinsHypoxiaKidneyMaleMiceMice, Inbred C57BLOxidantsOxidative StressAdenosine TriphosphateCaspasesEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHspa5 protein, mouseOxidantsProtective AgentsTunicamycin

Identifiers

PMID26444017
PMCPMC4596863

What OpenQuestion holds

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LicenceCC0
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.