AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD.

Brandauer J, Andersen MA, Kellezi H, Risis S, Frøsig C, Vienberg SG, Treebak JT

Frontiers in physiology24 Mar 2015Cited by 67 (Europe PMC)

PMID25852572PMCIDPMC4371692DOI10.3389/fphys.2015.00085PepBankPUB-25852572

Summary

The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS) handling. We determined the requirement of AMP-activated protein kinase (AMPK) for exercise training-induced increases in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p < 0.01) and superoxide dismutase 2 (MnSOD; p < 0.05) protein abundance in quadriceps muscle of wild-type (WT; n = 13-15), but not AMPK α2 kinase dead (KD; n = 12-13) mice. We also observed a strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of healthy humans (p = 0.051; n = 6). To further elucidate a role for AMPK in mediating these effects, we treated WT (n = 7-8) and AMPK α2 KD (n = 7-9) mice with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). Four weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK α2 KD mice. We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n = 9-10). Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p < 0.05). Finally, the acetylation status of SIRT3 target lysine residues on MnSOD (K122) or oligomycin-sensitivity conferring protein (OSCP; K139) was not altered in either mouse or human skeletal muscle in response to acute exercise. We propose an important role for AMPK in regulating mitochondrial function and ROS handling in skeletal muscle in response to exercise training.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone4

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

01AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, AICAR increased skeletal muscle SIRT3 in wild-type mice but not AMPK kinase-dead mice.
In plain wordsIn mice, AICAR increased muscle SIRT3 in normal mice but not mice with inactive AMPK.
Peptide
AICAR (acadesine)
Outcome
MixedSIRT3 after AICAR in WT and AMPK KD mice
Study
mousen: not reported in source
Wild-type and AMPK kinase-dead or PGC-1α knockout mice
Outcome group
Mitochondrial function · Musculoskeletal
Source sentences
Summary
Four weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK α2 KD mice.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2585257201
02AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, AICAR increased skeletal muscle MnSOD in wild-type mice but not AMPK kinase-dead mice.
In plain wordsIn mice, AICAR increased muscle MnSOD in normal mice but not mice with inactive AMPK.
Peptide
AICAR (acadesine)
Outcome
MixedMnSOD after AICAR in WT and AMPK KD mice
Study
mousen: not reported in source
Wild-type and AMPK kinase-dead or PGC-1α knockout mice
Outcome group
Mitochondrial function · Musculoskeletal
Source sentences
Summary
Four weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK α2 KD mice.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2585257202
03AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, repeated AICAR increased skeletal muscle SIRT3 only in wild-type mice, not PGC-1α knockout mice.
In plain wordsIn mice, AICAR increased muscle SIRT3 only when the PGC-1α gene was present.
Peptide
AICAR (acadesine)
Outcome
MixedSIRT3 response dependent on PGC-1α
Study
mousen: not reported in source
Wild-type and AMPK kinase-dead or PGC-1α knockout mice
Outcome group
Mitochondrial function · Musculoskeletal
Source sentences
Summary
Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n = 9-10).
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2585257203
04AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, repeated AICAR increased skeletal muscle MnSOD only in wild-type mice, not PGC-1α knockout mice.
In plain wordsIn mice, AICAR increased muscle MnSOD only when the PGC-1α gene was present.
Peptide
AICAR (acadesine)
Outcome
MixedMnSOD response dependent on PGC-1α
Study
mousen: not reported in source
Wild-type and AMPK kinase-dead or PGC-1α knockout mice
Outcome group
Mitochondrial function · Musculoskeletal
Source sentences
Summary
Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n = 9-10).
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2585257204

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.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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