Evidence map›Paper›PMID 26990160›Full record

ArticleInvestigative ophthalmology & visual science2016

The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction.

Parameswaran G Sreekumar, Keijiro Ishikawa, Chris Spee, Hemal H Mehta, Junxiang Wan, Kelvin Yen, Pinchas Cohen, Ram Kannan, David R Hinton

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
15.0field-weighted citation impact, top 1% 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

115 citing papers in PubMed, 172 citations in OpenAlex.

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  12. Mitochondrial regulation of cellular senescence heterogeneity.Frontiers in cell and developmental biology · 2026
    Review
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  15. Article
  16. Review
  17. Retinal progenitor cells (jCell) for retinitis pigmentosa.Frontiers in cellular neuroscience · 2025
    Article
  18. Review
  19. Review
  20. Article

55 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Parameswaran G SreekumarArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California, United States.
Keijiro IshikawaArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California, United States.
Chris SpeeDepartment of Ophthalmology, University of Southern California, Los Angeles, California, United States.
Hemal H MehtaUSC Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, United States.
Junxiang WanUSC Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, United States.
Kelvin YenUSC Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, United States.
Pinchas CohenUSC Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, United States.
Ram KannanArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California, United States.
David R HintonDepartment of Ophthalmology, University of Southern California, Los Angeles, California, United States 4Department of Pathology, University of Southern California, Los Angeles, California, United States.
University of Southern California · USDoheny Eye Institute · US

Funding

The Role of the Glucose-regulated Protein GRP78/BiP in Stress Resistance and AginP01AG034906 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LONGO, VALTER D. · 2011 to 2016
$9.3M
VISION RESEARCHP30EY003040 · NEI · DOHENY EYE INSTITUTE · PI SUN, DEMING · 1985 to 2013
$7.0M
EXPERIMENTAL APPROACH TO MACULOPATHYR01EY001545 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HINTON, DAVID R. · 1985 to 2016
$6.0M
Novel Mitochondrially Encoded Peptides and Their Role in Health and DiseaseR01GM090311 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS · 2009 to 2013
$3.2M
Plasma Mitochondrial Peptide Assays as Biomarkers of Environmental Toxin ExposureR01ES020812 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS · 2011 to 2015
$1.8M
A family of novel mitochondrially-encoded peptides and their role in agingR01AG034430 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS · 2009 to 2012
$1.2M
NEI NIH HHS EY01545NEI NIH HHS EY03040NEI NIH HHS P30 EY003040NEI NIH HHS R01 EY001545NIA NIH HHS 1P01AG034906NIA NIH HHS 1R01AG034430NIA NIH HHS P01 AG034906NIA NIH HHS R01 AG034430NIEHS NIH HHS 1R01ES020812NIEHS NIH HHS R01 ES020812NIGMS NIH HHS 1R01GM090311NIGMS NIH HHS R01 GM090311
6 · The paper itself

Abstract

purposeTo investigate the expression of humanin (HN) in human retinal pigment epithelial (hRPE) cells and its effect on oxidative stress-induced cell death, mitochondrial bioenergetics, and senescence.

methodsHumanin localization in RPE cells and polarized RPE monolayers was assessed by confocal microscopy. Human RPE cells were treated with 150 μM tert-Butyl hydroperoxide (tBH) in the absence/presence of HN (0.5-10 μg/mL) for 24 hours. Mitochondrial respiration was measured by XF96 analyzer. Retinal pigment epithelial cell death and caspase-3 activation, mitochondrial biogenesis and senescence were analyzed by TUNEL, immunoblot analysis, mitochondrial DNA copy number, SA-β-Gal staining, and p16INK4a expression and HN levels by ELISA. Oxidative stress-induced changes in transepithelial resistance were studied in RPE monolayers with and without HN cotreatment.

resultsA prominent localization of HN was found in the cytoplasmic and mitochondrial compartments of hRPE. Humanin cotreatment inhibited tBH-induced reactive oxygen species formation and significantly restored mitochondrial bioenergetics in hRPE cells. Exogenous HN was taken up by RPE and colocalized with mitochondria. The oxidative stress-induced decrease in mitochondrial bioenergetics was prevented by HN cotreatment. Humanin treatment increased mitochondrial DNA copy number and upregulated mitochondrial transcription factor A, a key biogenesis regulator protein. Humanin protected RPE cells from oxidative stress-induced cell death by STAT3 phosphorylation and inhibiting caspase-3 activation. Humanin treatment inhibited oxidant-induced senescence. Polarized RPE demonstrated elevated cellular HN and increased resistance to cell death.

conclusionsHumanin protected RPE cells against oxidative stress-induced cell death and restored mitochondrial function. Our data suggest a potential role for HN therapy in the prevention of retinal degeneration, including AMD.

Indexed as

Gene Expression Regulation, DevelopmentalApoptosisCells, CulturedCellular SenescenceHumansIn Situ Nick-End LabelingIntracellular Signaling Peptides and ProteinsMicroscopy, ConfocalMicroscopy, Electron, TransmissionMitochondriaOxidative StressPhosphorylationRetinal Pigment EpitheliumRNAhumaninIntracellular Signaling Peptides and ProteinsRNA

Identifiers

PMID26990160
PMCPMC4811181
OpenAlexW2319675468

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.