Evidence map›Paper›PMID 33989758›Full record

ArticleFree radical biology & medicine2021

Cellular antioxidant mechanisms control immunoglobulin light chain-mediated proximal tubule injury.

Kai Er Ying, Wenguang Feng, Wei-Zhong Ying, Paul W Sanders

Open access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 57% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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 1 institution in 1 country.

Kai Er YingDivision of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0007, USA.
Wenguang FengDivision of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0007, USA.
Wei-Zhong YingDivision of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0007, USA.
Paul W SandersDivision of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0007, USA; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, 35294-0007, USA; Department of Veterans Affairs Medical Center, Birmingham, AL, 35233, USA. Electronic address: psanders@uab.edu.
University of Alabama at Birmingham · US

Funding

UAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CURTIS, LISA M · 2008 to 2022
$18.3M
Low Molecular Weight Protein NephrotoxicityI01CX001326 · VA · BIRMINGHAM VA MEDICAL CENTER · PI SANDERS, PAUL W. · 2015 to 2024
–
BLRD VA I01 BX001192BLRD VA I01 BX005640CSRD VA I01 CX001326NIDDK NIH HHS P30 DK079337
6 · The paper itself

Abstract

A major cause of morbidity and mortality in multiple myeloma is kidney injury from overproduction of monoclonal immunoglobulin light chains (FLC). FLC can induce damage through the production of hydrogen peroxide, which activates pro-inflammatory and pro-apoptotic pathways. The present study focused on catalase, a highly conserved antioxidant enzyme that degrades hydrogen peroxide. Initial findings were that FLC increased hydrogen peroxide levels but also decreased catalase levels and activity in proximal tubule epithelium. In order to clarify, we showed that the phosphatidylinositol 3-kinase inhibitor, LY294002, inhibited FLC-induced Akt-mediated deactivation of Forkhead box O class 3a (FoxO3a) and increased catalase activity in proximal tubule cells. Augmented catalase activity decreased FLC-mediated production of hydrogen peroxide as well as the associated increase in High Mobility Group Box 1 (HMGB1) protein release and caspase-3 activity. Coincubation of cells with FLC and an allosteric activator of Sirtuin 1 (SIRT1) was also sufficient to increase catalase activity and promote similar cytoprotective effects. Our studies confirmed that the mechanism of downregulation of catalase by FLC involved deactivation of FoxO3a and inhibition of SIRT1. Mechanistic understanding of catalase regulation allows for future treatments that target pathways that increase catalase in the setting of proximal tubule injury from FLC.

Indexed as

AntioxidantsImmunoglobulin Light ChainsCatalaseHydrogen PeroxideKidney Tubules, ProximalAntioxidantsCatalaseHydrogen PeroxideImmunoglobulin Light ChainsCatalaseFoxO3aHMGB1Hydrogen peroxideProtein kinase BSirtuin 1STAT1

Identifiers

PMID33989758
PMCPMC8217262
OpenAlexW3161445926

What OpenQuestion holds

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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.