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Study · Animal study (in vivo) · mouse · 2024

6 results

Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms.

Amman AM, Wolfe V, Piraino G, Ziady A, Zingarelli B

Biomedicines15 Nov 2024

PMID39595179 (opens in a new tab)PMCIDPMC11592305 (opens in a new tab)DOI10.3390/biomedicines12112615 (opens in a new tab)PepBankPUB-39595179
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Summary

Background/Objectives: The severity of acute lung injury is significantly impacted by age and sex in patients with hemorrhagic shock. AMP-activated protein kinase (AMPK) is a crucial regulator of energy metabolism but its activity declines with aging. Humanin is a mitochondrial peptide that exerts cytoprotective effects in response to oxidative stressors and is associated with longevity. Using a mouse model of hemorrhagic shock that mimics the clinical condition of adult patients, we investigated whether treatment with a humanin analog, humanin-G, mitigates lung injury and whether its mechanisms of action are dependent on the catalytic AMPKα1 subunit activation. Methods: Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation. Results: Sex- and genotype-related differences were observed after hemorrhagic shock as lung neutrophil infiltration was more pronounced in the male AMPKα1 WT mice than the female WT mice; also, the male AMPKα1 KO mice experienced a significant decline in mean arterial blood pressure when compared to the male WT mice after resuscitation. The scores of histological lung injury were similarly elevated in all the male and female AMPKα1 WT and KO mice when compared to the control mice. At molecular analysis, acute lung injury was associated with the downregulation of AMPKα1/α2 catalytic subunits in the WT mice, whereas an increased activation of the signal transducer and activator of transcription-3 (STAT3) was observed in all the vehicle-treated groups. The in vivo administration of humanin-G ameliorated histological lung damage in all the groups of animals and ameliorated mean arterial blood pressure in the male AMPKα1 KO mice. The in vivo administration of humanin-G lowered lung neutrophil infiltration in the male and female AMPKα1 WT mice only but not in the KO mice. The beneficial results of humanin-G correlated with the lung cytosolic and nuclear activation of AMPKα in the male and female AMPKα1 WT groups, whereas STAT3 activation was not modified. Conclusions: In adult age, hemorrhage-induced acute lung injury manifests with sex-dependent characteristics. Humanin-G has therapeutic potential and the AMPKα1subunit is an important requisite for its inhibitory effects on lung leucosequestration, but not for the amelioration of lung alveolar structure or the hemodynamic effects of the peptide.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with hemorrhagic shock, humanin-G ameliorated histological lung damage in all the groups of animals.

    In plain wordsIn mice after blood loss, humanin-G reduced lung tissue damage in all groups.

    Peptide
    Humanin
    Outcome
    DecreaseHistological lung damage
    Study

    mousen: not reported in source

    Hemorrhagic shock with resuscitation
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The in vivo administration of humanin-G ameliorated histological lung damage in all the groups of animals
    1 context sentence
    Summary · context
    Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In male AMPKα1 knock-out mice after hemorrhagic shock, humanin-G ameliorated mean arterial blood pressure.

    In plain wordsIn male mice lacking AMPKα1 after blood loss, humanin-G improved blood pressure.

    Peptide
    Humanin
    Outcome
    IncreaseMean arterial blood pressure in male AMPKα1 KO mice
    Study

    mousen: not reported in source

    Hemorrhagic shock with resuscitation
    Comparator
    Vehicle
    Outcome group
    Blood pressure · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    and ameliorated mean arterial blood pressure in the male AMPKα1 KO mice.
    1 context sentence
    Summary · context
    Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In male and female AMPKα1 wild-type mice after hemorrhagic shock, humanin-G lowered lung neutrophil infiltration.

    In plain wordsIn normal male and female mice after blood loss, humanin-G lowered the number of neutrophils in the lungs.

    Peptide
    Humanin
    Outcome
    DecreaseLung neutrophil infiltration in AMPKα1 WT mice
    Study

    mousen: not reported in source

    Hemorrhagic shock with resuscitation
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The in vivo administration of humanin-G lowered lung neutrophil infiltration in the male and female AMPKα1 WT mice
    1 context sentence
    Summary · context
    Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In AMPKα1 knock-out mice after hemorrhagic shock, humanin-G did not lower lung neutrophil infiltration.

    In plain wordsIn mice lacking AMPKα1 after blood loss, humanin-G did not lower neutrophils in the lungs.

    Peptide
    Humanin
    Outcome
    No significant changeLung neutrophil infiltration in AMPKα1 KO mice
    Study

    mousen: not reported in source

    Hemorrhagic shock with resuscitation
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The in vivo administration of humanin-G lowered lung neutrophil infiltration in the male and female AMPKα1 WT mice only but not in the KO mice.
    1 context sentence
    Summary · context
    Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In male and female AMPKα1 wild-type mice, the benefits of humanin-G correlated with cytosolic and nuclear activation of AMPKα in the lung.

    In plain wordsIn normal mice after blood loss, the lung benefits of humanin-G were linked to more AMPKα activity.

    Peptide
    Humanin
    Outcome
    IncreaseLung AMPKα activation
    Study

    mousen: not reported in source

    Hemorrhagic shock with resuscitation
    Comparator
    Vehicle
    Outcome group
    Receptor activity and mechanism · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The beneficial results of humanin-G correlated with the lung cytosolic and nuclear activation of AMPKα in the male and female AMPKα1 WT groups
    1 context sentence
    Summary · context
    Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In mice with hemorrhagic shock, humanin-G did not modify STAT3 activation in the lung.

    In plain wordsIn mice after blood loss, humanin-G did not change STAT3 activity in the lungs.

    Peptide
    Humanin
    Outcome
    No significant changeLung STAT3 activation
    Study

    mousen: not reported in source

    Hemorrhagic shock with resuscitation
    Comparator
    Vehicle
    Outcome group
    Receptor activity and mechanism · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    whereas STAT3 activation was not modified.
    1 context sentence
    Summary · context
    Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8-13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer's solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation.

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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