Evidence map›Paper›PMID 18502748›Full record

ArticleThe Journal of biological chemistry2008

Oxidative inactivation of the proteasome in retinal pigment epithelial cells. A potential link between oxidative stress and up-regulation of interleukin-8.

Alexandre F Fernandes, Jilin Zhou, Xinyu Zhang, Qingning Bian, Janet Sparrow, Allen Taylor, Paulo Pereira, Fu Shang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.4field-weighted citation impact, top 7% 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

42 citing papers in PubMed, 68 citations in OpenAlex.

  1. Trial
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  3. The Role of the Ubiquitin System in Eye Diseases.Life (Basel, Switzerland) · 2025
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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

8 authors at 5 institutions in 2 countries.

Alexandre F FernandesJean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Jilin Zhou
Xinyu Zhang
Qingning Bian
Janet Sparrow
Allen Taylor
Paulo Pereira
Fu Shang
Columbia University · USUnited States Department of Agriculture · USUniversity of Coimbra · PTJean Mayer Human Nutrition Research Center on Aging · USTufts University · US

Funding

IMPACT OF LIPOFUSCIN IN RETINAL PIGMENT EPITHELIAL CELLSR01EY012951 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SPARROW, JANET RUTHE · 2000 to 2024
$8.9M
Ubiquitin Function In Eye LensR01EY013250 · NEI · TUFTS UNIVERSITY BOSTON · PI TAYLOR, ALLEN · 2001 to 2012
$4.0M
Role of ubiqutin in quality control of lens proteinsR01EY011717 · NEI · TUFTS UNIVERSITY BOSTON · PI SHANG, FU · 2003 to 2010
$1.8M
UBIQUITIN DEPENDENT PATHWAY AND LENS EPITHELIUMR29EY011717 · NEI · TUFTS UNIVERSITY BOSTON · PI SHANG, FU · 1998 to 2002
$381k
NEI NIH HHS EY 11717NEI NIH HHS EY 12951NEI NIH HHS EY 13250
6 · The paper itself

Abstract

Oxidative stress and inflammation are implicated in the pathogenesis of many age-related diseases. Stress-induced overproduction of inflammatory cytokines, such as interleukin-8 (IL-8), is one of the early events of inflammation. The objective of this study was to elucidate mechanistic links between oxidative stress and overproduction of IL-8 in retinal pigment epithelial (RPE) cells. We found that exposure of RPE cells to H(2)O(2), paraquat, or A2E-mediated photooxidation resulted in increased expression and secretion of IL-8. All of these oxidative stressors also inactivated the proteasome in RPE cells. In contrast, tert-butylhydroperoxide (TBH), a lipophilic oxidant that did not stimulate IL-8 production, also did not inactivate the proteasome. Moreover, prolonged treatment of RPE cells with proteasome-specific inhibitors recapitulated the stimulation of IL-8 production. These data suggest that oxidative inactivation of the proteasome is a potential mechanistic link between oxidative stress and up-regulation of the proinflammatory IL-8. The downstream signaling pathways that govern the production of IL-8 include NF-kappaB and p38 MAPK. Proteasome inhibition both attenuated the activation and delayed the turnoff of NF-kappaB, resulting in biphasic effects on the production of IL-8. Prolonged proteasome inhibition (>2 h) resulted in activation of p38 MAPK via activation of MKK3/6 and increased the production of IL-8. Chemically inhibiting the p38 MAPK blocked the proteasome inhibition-induced up-regulation of IL-8. Together, these data indicate that oxidative inactivation of the proteasome and the related activation of the p38 MAPK pathway provide a potential link between oxidative stress and overproduction of proinflammatory cytokines, such as IL-8.

Indexed as

Gene Expression RegulationCell LineEpithelial CellsGene Expression Regulation, EnzymologicHumansHydrogen PeroxideInflammationInterleukin-8LightModels, BiologicalOxidative StressOxygenPigment Epithelium of EyeProteasome Endopeptidase ComplexTime FactorsHydrogen PeroxideInterleukin-8OxygenProteasome Endopeptidase Complex

Identifiers

PMID18502748
PMCPMC2475710
OpenAlexW1987706913

What OpenQuestion holds

Textmetadata
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.