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Study · In vitro (cells) · 2016

8 results

Humanin Protects RPE Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Upregulation of Mitochondrial Glutathione.

Matsunaga D, Sreekumar PG, Ishikawa K, Terasaki H, Barron E, Cohen P, Kannan R, Hinton DR

PloS one26 Oct 2016Cited by 51 (Europe PMC)

PMID27783653 (opens in a new tab)PMCIDPMC5081188 (opens in a new tab)DOI10.1371/journal.pone.0165150 (opens in a new tab)PepBankPUB-27783653
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Summary

Humanin (HN) is a small mitochondrial-encoded peptide with neuroprotective properties. We have recently shown protection of retinal pigmented epithelium (RPE) cells by HN in oxidative stress; however, the effect of HN on endoplasmic reticulum (ER) stress has not been evaluated in any cell type. Our aim here was to study the effect of HN on ER stress-induced apoptosis in RPE cells with a specific focus on ER-mitochondrial cross-talk. Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL). All three ER stressors induced RPE cell apoptosis in a dose dependent manner. HN pretreatment significantly decreased the number of apoptotic cells with all three ER stressors in a dose dependent manner. HN pretreatment similarly protected U-251 glioma cells from TM-induced apoptosis in a dose dependent manner. HN pretreatment significantly attenuated activation of caspase 3 and ER stress-specific caspase 4 induced by TM. TM treatment increased mitochondrial superoxide production, and HN co-treatment resulted in a decrease in mitochondrial superoxide compared to TM treatment alone. We further showed that depleted mitochondrial glutathione (GSH) levels induced by TM were restored with HN co-treatment. No significant changes were found for the expression of several antioxidant enzymes between TM and TM plus HN groups except for the expression of glutamylcysteine ligase catalytic subunit (GCLC), the rate limiting enzyme required for GSH biosynthesis, which is upregulated with TM and TM+HN treatment. These results demonstrate that ER stress promotes mitochondrial alterations in RPE that lead to apoptosis. We further show that HN has a protective effect against ER stress-induced apoptosis by restoring mitochondrial GSH. Thus, HN should be further evaluated for its therapeutic potential in disorders linked to ER stress.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Efficacy outcome

    In primary human RPE cells, humanin pretreatment decreased apoptotic cells with tunicamycin, brefeldin A and thapsigargin in a dose dependent manner.

    In plain wordsIn lab tests on human eye cells, humanin pretreatment reduced cell death caused by three different stress-inducing chemicals.

    Peptide
    Humanin
    Outcome
    DecreaseApoptotic RPE cells after ER stressors
    Study

    humann: not reported in source

    Primary human RPE cells
    Comparator
    ER stressor without HN
    Outcome group
    Neuroprotection · Eye
    Studied dose
    1-20 μg/mL · 12 hr pretreatmentAs given in this study (human).

    Source sentences

    Summary
    HN pretreatment significantly decreased the number of apoptotic cells with all three ER stressors in a dose dependent manner.
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).
  2. 02LabIn vitro (cells)Efficacy outcome

    In U-251 glioma cells, humanin pretreatment protected from tunicamycin-induced apoptosis in a dose dependent manner.

    In plain wordsIn lab tests on glioma cells, humanin pretreatment protected the cells from death caused by a stress-inducing chemical.

    Peptide
    Humanin
    Outcome
    DecreaseApoptosis of U-251 glioma cells after tunicamycin
    Study

    n: not reported in source

    U-251 glioma cells
    Comparator
    Tunicamycin without HN
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    HN pretreatment similarly protected U-251 glioma cells from TM-induced apoptosis in a dose dependent manner.
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).
  3. 03LabIn vitro (cells)Mechanism

    In primary human RPE cells, humanin pretreatment attenuated caspase 3 activation induced by tunicamycin.

    In plain wordsIn lab tests on human eye cells, humanin pretreatment reduced activation of caspase 3, a cell death enzyme.

    Peptide
    Humanin
    Outcome
    DecreaseCaspase 3 activation after tunicamycin
    Study

    humann: not reported in source

    Primary human RPE cells
    Comparator
    Tunicamycin without HN
    Outcome group
    Neuroprotection · Eye
    Studied dose
    1-20 μg/mL · 12 hr pretreatmentAs given in this study (human).

    Source sentences

    Summary
    HN pretreatment significantly attenuated activation of caspase 3 and ER stress-specific caspase 4 induced by TM.
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).
  4. 04LabIn vitro (cells)Mechanism

    In primary human RPE cells, humanin pretreatment attenuated activation of ER stress-specific caspase 4 induced by tunicamycin.

    In plain wordsIn lab tests on human eye cells, humanin pretreatment reduced activation of caspase 4, a stress-linked cell death enzyme.

    Peptide
    Humanin
    Outcome
    DecreaseER stress-specific caspase 4 activation after tunicamycin
    Study

    humann: not reported in source

    Primary human RPE cells
    Comparator
    Tunicamycin without HN
    Outcome group
    Neuroprotection · Eye
    Studied dose
    1-20 μg/mL · 12 hr pretreatmentAs given in this study (human).

    Source sentences

    Summary
    HN pretreatment significantly attenuated activation of caspase 3 and ER stress-specific caspase 4 induced by TM.
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).
  5. 05LabIn vitro (cells)Mechanism

    In primary human RPE cells, humanin co-treatment decreased mitochondrial superoxide compared with tunicamycin alone.

    In plain wordsIn lab tests on human eye cells, humanin reduced mitochondrial superoxide compared with the stress chemical alone.

    Peptide
    Humanin
    Outcome
    DecreaseMitochondrial superoxide production
    Study

    humann: not reported in source

    Primary human RPE cells
    Comparator
    Tunicamycin alone
    Outcome group
    Mitochondrial function · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    TM treatment increased mitochondrial superoxide production, and HN co-treatment resulted in a decrease in mitochondrial superoxide compared to TM treatment alone.
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).
  6. 06LabIn vitro (cells)Mechanism

    In primary human RPE cells, humanin co-treatment restored mitochondrial glutathione levels depleted by tunicamycin.

    In plain wordsIn lab tests on human eye cells, humanin restored mitochondrial glutathione that the stress chemical had depleted.

    Peptide
    Humanin
    Outcome
    IncreaseMitochondrial glutathione levels
    Study

    humann: not reported in source

    Primary human RPE cells
    Comparator
    Tunicamycin alone
    Outcome group
    Mitochondrial function · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We further showed that depleted mitochondrial glutathione (GSH) levels induced by TM were restored with HN co-treatment.
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).
  7. 07LabIn vitro (cells)Mechanism

    In primary human RPE cells, humanin did not significantly change the expression of several antioxidant enzymes between tunicamycin alone and tunicamycin with humanin.

    In plain wordsIn lab tests on human eye cells, adding humanin did not significantly change levels of several antioxidant enzymes.

    Peptide
    Humanin
    Outcome
    No significant changeAntioxidant enzyme expression, TM versus TM plus HN
    Study

    humann: not reported in source

    Primary human RPE cells
    Comparator
    Tunicamycin alone
    Outcome group
    Mitochondrial function · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    No significant changes were found for the expression of several antioxidant enzymes between TM and TM plus HN groups
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).
  8. 08LabIn vitro (cells)Mechanism

    In primary human RPE cells, GCLC, the rate limiting enzyme for glutathione synthesis, was upregulated with tunicamycin and with tunicamycin and humanin together.

    In plain wordsIn lab tests on human eye cells, an enzyme needed to make glutathione rose with the stress chemical, with or without humanin.

    Peptide
    Humanin
    Outcome
    Not applicableGCLC expression with tunicamycin and tunicamycin plus HN
    Study

    humann: not reported in source

    Primary human RPE cells
    Comparator
    Tunicamycin alone
    Outcome group
    Mitochondrial function · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    except for the expression of glutamylcysteine ligase catalytic subunit (GCLC), the rate limiting enzyme required for GSH biosynthesis, which is upregulated with TM and TM+HN treatment.
    1 context sentence
    Summary · context
    Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

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