Evidence map›Paper›PMID 27364765›Full record

ArticleScientific reports2016

A novel AhR ligand, 2AI, protects the retina from environmental stress.

Mark A Gutierrez, Sonnet S Davis, Andrew Rosko, Steven M Nguyen, Kylie P Mitchell, Samiha Mateen, Joana Neves, Thelma Y Garcia, Shaun Mooney, Gary H Perdew and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  14. The Aryl Hydrocarbon Receptor and the Nervous System.International journal of molecular sciences · 2018
    Review
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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

13 authors at 4 institutions in 1 country.

Mark A GutierrezUniversity of Denver, Colorado 2199 S University Blvd, Denver, CO 80208, USA.
Sonnet S DavisBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Andrew RoskoBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Steven M NguyenBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Kylie P MitchellBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Samiha MateenBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Joana NevesBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Thelma Y GarciaBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Shaun MooneyUniversity of Washington Box 358047 Seattle, WA 98195, USA.
Gary H PerdewThe Pennsylvania State University, Center for Molecular Toxicology and Carcinogenesis, 309 Life Sciences Building, University Park, PA 16802, USA.
Troy D HubbardThe Pennsylvania State University, Center for Molecular Toxicology and Carcinogenesis, 309 Life Sciences Building, University Park, PA 16802, USA.
Deepak A LambaBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Arvind RamanathanBuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94901, USA.
Buck Institute for Research on Aging · USPennsylvania State University · USUniversity of Denver · USUniversity of Washington · US

Funding

REGULATION OF THE AH RECEPTORR01ES004869 · NIEHS · PURDUE UNIVERSITY WEST LAFAYETTE · PI PERDEW, GARY H. · 1994 to 2017
$5.3M
NIEHS NIH HHS R01 ES004869
6 · The paper itself

Abstract

Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2'-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice.

Indexed as

AldehydesAnimalsApoptosisCell LineFatty Acids, UnsaturatedHumansIndolesLigandsLightLipid PeroxidationMiceMice, Inbred BALB CMice, Inbred C57BLPolychlorinated DibenzodioxinsProtective AgentsReactive Oxygen Species4-hydroxy-2-nonenalAldehydesFatty Acids, UnsaturatedIndolesLigandsPolychlorinated DibenzodioxinsProtective AgentsReactive Oxygen SpeciesReceptors, Aryl HydrocarbonRNA, Small Interfering

Identifiers

PMID27364765
PMCPMC4929558
OpenAlexW2460592200

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.