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Study · Animal study (in vivo) · mouse · 2012

5 results

AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation.

Lanner JT, Georgiou DK, Dagnino-Acosta A, Ainbinder A, Cheng Q, Joshi AD, Chen Z, Yarotskyy V, Oakes JM, Lee CS, Monroe TO, Santillan A and 6 more

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Dong K, Goodyear L, Ismailov II, Rodney GG, Dirksen RT, Hamilton SL

Nature medicine8 Jan 2012Cited by 100 (Europe PMC)

PMID22231556 (opens in a new tab)PMCIDPMC3274651 (opens in a new tab)DOI10.1038/nm.2598 (opens in a new tab)PepBankPUB-22231556
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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study5

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In Ryr1-mutant mice, AICAR prevented heat-induced sudden death.

    In plain wordsIn mice with mutant Ryr1, AICAR prevented heat-induced sudden death.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseHeat-induced death
    Study

    mousen: not reported in source

    Ryr1 Y524S knock-in mice
    Outcome group
    Mortality · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show here that treatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) prevents this heat-induced sudden death in this mouse model.
    2 context sentences
    Summary · context
    Although antioxidants are effective in reducing this cycle in vitro, only AICAR prevents heat-induced death in vivo.
    Summary · context
    Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C).
  2. 02AnimalAnimal study (in vivo)Mechanism

    In Ryr1-mutant mice, protection by AICAR was independent of AMPK activation.

    In plain wordsIn mice with mutant Ryr1, AICAR protection did not depend on AMPK activation.

    Peptide
    AICAR (acadesine)
    Outcome
    Not applicableAMPK dependence of protection
    Study

    mousen: not reported in source

    Ryr1 Y524S knock-in mice
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The protection by AICAR is independent of AMP-activated protein kinase (AMPK) activation
    1 context sentence
    Summary · context
    Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C).
  3. 03AnimalAnimal study (in vivo)Mechanism

    In the mutant Ryr1 model, AICAR reduced calcium leak from the sarcoplasmic reticulum.

    In plain wordsIn mice with mutant Ryr1, AICAR reduced calcium leakage from muscle calcium stores.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseSarcoplasmic reticulum calcium leak
    Study

    mousen: not reported in source

    Ryr1 Y524S knock-in mice
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The protection by AICAR is independent of AMP-activated protein kinase (AMPK) activation and results from a newly identified action of the compound on mutant Ryr1 to reduce Ca(2+) leak from the sarcoplasmic reticulum to the sarcoplasm.
    1 context sentence
    Summary · context
    Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C).
  4. 04AnimalAnimal study (in vivo)Mechanism

    In the mutant Ryr1 model, AICAR prevented calcium-dependent increases in ROS.

    In plain wordsIn mice with mutant Ryr1, AICAR prevented calcium-dependent increases in reactive oxygen species.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseReactive oxygen species
    Study

    mousen: not reported in source

    Ryr1 Y524S knock-in mice
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AICAR thus prevents Ca(2+)-dependent increases in the amount of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) that act to further increase resting Ca(2+) concentrations.
    1 context sentence
    Summary · context
    Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C).
  5. 05AnimalAnimal study (in vivo)Mechanism

    In the mutant Ryr1 model, AICAR prevented calcium-dependent increases in RNS.

    In plain wordsIn mice with mutant Ryr1, AICAR prevented calcium-dependent increases in reactive nitrogen species.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseReactive nitrogen species
    Study

    mousen: not reported in source

    Ryr1 Y524S knock-in mice
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AICAR thus prevents Ca(2+)-dependent increases in the amount of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) that act to further increase resting Ca(2+) concentrations.
    1 context sentence
    Summary · context
    Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C).

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

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

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