Evidence map›Paper›PMID 23841471›Full record

ArticleCurrent eye research2013

Differential effects of the estrogen receptor agonist estradiol on toxicity induced by enzymatically-derived or autoxidation-derived oxysterols in human ARPE-19 cells.

Bhanu Dasari, Jaya R P Prasanthi, Craig Meiers, Brij B Singh, Othman Ghribi

Open access · greenAbstract read
In one paragraph

Article in Current eye research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. 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

5 authors at 1 institution in 1 country.

Bhanu DasariDepartment of Pharmacology, Physiology and Therapeutics and.
Jaya R P Prasanthi
Craig Meiers
Brij B Singh
Othman Ghribi
University of North Dakota · US

Funding

TRPC1, Calcium, and Saliva SecretionR01DE017102 · NIDCR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Brij B Singh · 2006 to 2026
$7.5M
Cholesterol induces oxidative stress and triggers iron and A? accumulationR01ES014826 · NIEHS · UNIVERSITY OF NORTH DAKOTA · PI GHRIBI, OTHMAN · 2008 to 2012
$1.5M
NIDCR NIH HHS R01 DE017102NIEHS NIH HHS R01 ES014826NIEHS NIH HHS R01ES014826
6 · The paper itself

Abstract

purpose/aim of the studyDisturbances in cholesterol metabolism and increased levels of cholesterol oxidation products (oxysterols) in retina may contribute to age-related macular degeneration (AMD). The role of oxysterols or of their target receptors liver X receptors (LXRs) and estrogen receptors (ERs) in the pathogenesis of MD is ill-known. The purpose of this study is to determine the extent to which the oxysterols 27-hydroxycholesterol (27-OHC), 25-hydroxycholesterol (25-OHC) and 7-ketocholesterol (7-KC) affect the transcriptional activity of LXR and ER. MATERIALS AND

methodsARPE-19 cells, untreated or incubated with 27-OHC, 25-OHC or 7-KC for 24 h were harvested. We used Western blot analyses for detecting ERs and LXRs expression, dual luciferase assays for measuring LXRs and ERs transcriptional activity, cytotox-ONE homogeneous membrane integrity assay for measuring cytotoxicity, JC-1 method for measuring mitochondrial membrane potential changes and ELISA for measuring cytokine levels.

resultsBoth LXRs and ERs are expressed and are transcriptionally active in ARPE-19 cells. 27-OHC, 25-OHC and 7-KC inhibited ER-mediated transcriptional activity, whereas 27-OHC and 25-OHC increased LXR-mediated transcription. E2 reduced 25-OHC and 27-OHC-induced cytotoxicity, mitochondrial permeability potential decline, and cytokine secretion. The LXR agonist GW3965 or the LXR antagonist 5α-6α-epoxycholesterol-3-sulfate (ECHS) did not offer protection against either 27-OHC and 25-OHC or 7-KC.

conclusionsIncreased levels of oxysterols can decrease ER and increase LXR signaling. ER agonists can offer protection against cytotoxic effects of 27-OHC and 25-OHC, two oxysterols derived by enzymatic reactions. Although they exert similar toxicity, the cellular mechanisms involved in the toxic effects of oxysterols whether derived by enzymatic or autoxidation reactions appear to be different.

Indexed as

Cell LineChemokine CCL2Drug InteractionsEstradiolEstrogen Receptor alphaEstrogen Receptor betaHumansHydroxycholesterolsInterleukin-6Interleukin-8KetocholesterolsLiver X ReceptorsMacular DegenerationOrphan Nuclear ReceptorsOxidation-ReductionPlatelet-Derived Growth Factor25-hydroxycholesterol27-hydroxycholesterol7-ketocholesterolCCL2 protein, humanChemokine CCL2CXCL8 protein, humanESR1 protein, humanEstradiolEstrogen Receptor alphaEstrogen Receptor betaHydroxycholesterolsIL6 protein, humanInterleukin-6Interleukin-8KetocholesterolsLiver X ReceptorsOrphan Nuclear ReceptorsPlatelet-Derived Growth FactorTumor Necrosis Factor-alphaVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID23841471
PMCPMC4067899
OpenAlexW2039909947

What OpenQuestion holds

Textmetadata
LicenceTDM
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.