Evidence map›Paper›PMID 36575190›Full record

ArticleScientific reports2022

Pretreatment of human retinal pigment epithelial cells with sterculic acid forestalls fenretinide-induced apoptosis.

Samuel William, Todd Duncan, T Michael Redmond

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 47% 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

3 citing papers in PubMed, 3 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

3 authors at 1 institution in 1 country.

Samuel WilliamLaboratory of Retinal Cell and Molecular Biology, Bldg. 6/Room 112A, National Eye Institute, National Institutes of Health, 6 Center Drive, Bethesda, MD, 20892-0608, USA. samuelw@nei.nih.gov.
Todd DuncanLaboratory of Retinal Cell and Molecular Biology, Bldg. 6/Room 112A, National Eye Institute, National Institutes of Health, 6 Center Drive, Bethesda, MD, 20892-0608, USA.
T Michael RedmondLaboratory of Retinal Cell and Molecular Biology, Bldg. 6/Room 112A, National Eye Institute, National Institutes of Health, 6 Center Drive, Bethesda, MD, 20892-0608, USA.
National Institutes of Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ratio of saturated to monounsaturated fatty acids, thought to play a critical role in many cellular functions, is regulated by stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids. Previously, we observed a decrease in both SCD protein and enzymatic activity in apoptosis induced by fenretinide, a synthetic analog of retinoic acid, in the human retinal pigment epithelial (RPE) cell line ARPE-19. Here, we investigated the effect of pretreating ARPE-19 with sterculic acid, a cyclopropenoic fatty acid inhibitor of SCD, on preventing fenretinide-induced apoptosis, given the role of SCD in cell proliferation and apoptosis. We show that sterculic acid pretreatment prevents the effects of fenretinide-induced apoptosis shown by changes in cell morphology, viability, and caspase-3 activation. Analysis of endoplasmic reticulum (ER)-associated proteins shows that sterculic acid pretreatment reduced the fenretinide-induced upregulation of heme oxygenase-1, ATF3 and GADD153 expression that are in response to reactive oxygen species (ROS) generation. Sterculic acid is as effective as allopurinol in inhibition of xanthine oxidase (XDH), and this may play a role in reducing the potential role of XDH in fenretinide-induced ROS generation. Sterculic acid pretreatment also results in a reduction in SOD2 mRNA expression. Dihydroceramide accumulation, compared to ceramide, and ROS generation indicate that a ceramide-independent pathway mediates fenretinide-induced apoptosis, and ROS mediation is borne out by activation of the NF-κBp50 and NF-κBp65 downstream signaling cascade. Its prevention by sterculic acid pretreatment further indicates the latter's antioxidant/anti-inflammatory effect. Taken together, our results suggest that sterculic acid pretreatment can mitigate ROS-mediated fenretinide-induced apoptosis. Thus, sterculic acid may serve as a potential antioxidant and therapeutic agent. These effects may be independent of its effects on SCD activity.

Indexed as

FenretinideAntioxidantsApoptosisCeramidesCyclopropanesEpithelial CellsFatty Acids, MonounsaturatedHumansReactive Oxygen SpeciesRetinal PigmentsAntioxidantsCeramidesCyclopropanesFatty Acids, MonounsaturatedFenretinideReactive Oxygen SpeciesRetinal Pigmentssterculic acid

Identifiers

PMID36575190
PMCPMC9794835
OpenAlexW4313252015

What OpenQuestion holds

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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.