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Study · Animal study (in vivo) · mouse · 2016

7 results

The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus.

Kim SJ, Guerrero N, Wassef G, Xiao J, Mehta HH, Cohen P, Yen K

Oncotarget1 Jul 2016Cited by 79 (Europe PMC)

PMID27384491 (opens in a new tab)PMCIDPMC5216912 (opens in a new tab)DOI10.18632/oncotarget.10380 (opens in a new tab)PepBankPUB-27384491
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Summary

Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively. Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus. These findings uncover a key signaling pathway of humanin that is important for humanin's function and also demonstrates an age-specific in vivo effect in a region of the brain that is critical for memory formation in an age-dependent manner.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In old mice, injected humanin increased AKT phosphorylation in the hippocampus.

    In plain wordsIn old mice, humanin injection raised AKT activation in the hippocampus, a brain area for memory.

    Peptide
    Humanin
    Outcome
    IncreaseAKT phosphorylation in hippocampus of old mice
    Study

    mousen: not reported in source

    Old mice, hippocampus
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In old mice, injected humanin increased ERK1/2 phosphorylation in the hippocampus.

    In plain wordsIn old mice, humanin injection raised ERK1/2 activation in the hippocampus, a brain area for memory.

    Peptide
    Humanin
    Outcome
    IncreaseERK1/2 phosphorylation in hippocampus of old mice
    Study

    mousen: not reported in source

    Old mice, hippocampus
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In young mice, injected humanin did not increase AKT or ERK1/2 phosphorylation in the hippocampus.

    In plain wordsIn young mice, humanin injection did not raise AKT or ERK1/2 activation in the hippocampus.

    Peptide
    Humanin
    Outcome
    No significant changeAKT and ERK1/2 phosphorylation in hippocampus of young mice
    Study

    mousen: not reported in source

    Young mice, hippocampus
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus.
  4. 04LabIn vitro (cells)Mechanism

    In cells, humanin acted through the GP130/IL6ST receptor complex to activate AKT, ERK1/2 and STAT3 signaling pathways.

    In plain wordsIn lab tests on cells, humanin worked through the GP130/IL6ST receptor to switch on three signaling pathways.

    Peptide
    Humanin
    Outcome
    Not applicableSignaling through the GP130/IL6ST receptor complex
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways.
  5. 05LabIn vitro (cells)Mechanism

    In cells, humanin treatment increased AKT phosphorylation, with PI3K involved.

    In plain wordsIn lab tests on cells, humanin raised AKT activation, and PI3K took part.

    Peptide
    Humanin
    Outcome
    IncreaseAKT phosphorylation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively.
  6. 06LabIn vitro (cells)Mechanism

    In cells, humanin treatment increased ERK 1/2 phosphorylation, with MEK involved.

    In plain wordsIn lab tests on cells, humanin raised ERK1/2 activation, and MEK took part.

    Peptide
    Humanin
    Outcome
    IncreaseERK1/2 phosphorylation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively.
  7. 07LabIn vitro (cells)Mechanism

    In cells, humanin treatment increased STAT3 phosphorylation, with JAK involved.

    In plain wordsIn lab tests on cells, humanin raised STAT3 activation, and JAK took part.

    Peptide
    Humanin
    Outcome
    IncreaseSTAT3 phosphorylation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively.

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

Subjects

Terms as the source lists them.

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