Acute activation of AMP-activated protein kinase prevents H2O2-induced premature senescence in primary human keratinocytes.

Ido Y, Duranton A, Lan F, Cacicedo JM, Chen TC, Breton L, Ruderman NB

PloS one13 Apr 2012Cited by 35 (Europe PMC)

PMID22514710PMCIDPMC3325987DOI10.1371/journal.pone.0035092PepBankPUB-22514710

Summary

We investigated the effects of AMPK on H(2)O(2)-induced premature senescence in primary human keratinocytes. Incubation with 50 µM H(2)O(2) for 2 h resulted in premature senescence with characteristic increases in senescence-associated ß-galactosidase (SA-gal) staining 3 days later and no changes in AMPK or p38 MAPK activity. The increase in SA-gal staining was preceded by increases in both p53 phosphorylation (S15) (1 h) and transactivation (6 h) and the abundance of the cyclin inhibitor p21(CIP1) (16 h). Incubation with AICAR or resveratrol, both of which activated AMPK, prevented the H(2)O(2)-induced increases in both SA-Gal staining and p21 abundance. In addition, AICAR diminished the increase in p53 transactivation. The decreases in SA-Gal expression induced by resveratrol and AICAR were prevented by the pharmacological AMPK inhibitor Compound C, expression of a DN-AMPK or AMPK knock-down with shRNA. Likewise, both knockdown of AMPK and expression of DN-AMPK were sufficient to induce senescence, even in the absence of exogenous H(2)O(2). As reported by others, we found that AMPK activation by itself increased p53 phosphorylation at S15 in embryonic fibroblasts (MEF), whereas under the same conditions it decreased p53 phosphorylation in the keratinocytes, human aortic endothelial cells, and human HT1080 fibrosarcoma cells. In conclusion, the results indicate that H(2)O(2) at low concentrations causes premature senescence in human keratinocytes by activating p53-p21(CIP1) signaling and that these effects can be prevented by acute AMPK activation and enhanced by AMPK downregulation. They also suggest that this action of AMPK may be cell or context-specific.

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

Results from this study5

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

01LabIn vitro (cells)Mechanism
In primary human keratinocytes, AICAR activated AMPK.
In plain wordsIn cells, AICAR activated AMPK in primary human keratinocytes.
Peptide
AICAR (acadesine)
Outcome
IncreaseAMPK activation
Study
humann: not reported in source
primary human keratinocytes challenged with H2O2
Outcome group
Receptor activity and mechanism · Skin and wound
Studied dose
Dose not stated
Source sentences
Summary
Incubation with AICAR or resveratrol, both of which activated AMPK, prevented the H(2)O(2)-induced increases in both SA-Gal staining and p21 abundance.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of AMPK on H(2)O(2)-induced premature senescence in primary human keratinocytes.
Show in the study text Report a problemFND-2251471001
02LabIn vitro (cells)Mechanism
In primary human keratinocytes, AICAR prevented the H2O2-induced increase in SA-Gal staining.
In plain wordsIn cells, AICAR prevented the increase in SA-Gal staining compared with H2O2 alone.
Peptide
AICAR (acadesine)
Outcome
DecreaseSA-Gal staining
Study
humann: not reported in source
primary human keratinocytes challenged with H2O2
Comparator
H2O2 without AICAR
Outcome group
Aging markers · Skin and wound
Studied dose
Dose not stated
Source sentences
Summary
Incubation with AICAR or resveratrol, both of which activated AMPK, prevented the H(2)O(2)-induced increases in both SA-Gal staining and p21 abundance.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of AMPK on H(2)O(2)-induced premature senescence in primary human keratinocytes.
Show in the study text Report a problemFND-2251471002
03LabIn vitro (cells)Mechanism
In primary human keratinocytes, AICAR prevented the H2O2-induced increase in p21 abundance.
In plain wordsIn cells, AICAR prevented the increase in p21 abundance compared with H2O2 alone.
Peptide
AICAR (acadesine)
Outcome
Decreasep21 abundance
Study
humann: not reported in source
primary human keratinocytes challenged with H2O2
Comparator
H2O2 without AICAR
Outcome group
Aging markers · Skin and wound
Studied dose
Dose not stated
Source sentences
Summary
Incubation with AICAR or resveratrol, both of which activated AMPK, prevented the H(2)O(2)-induced increases in both SA-Gal staining and p21 abundance.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of AMPK on H(2)O(2)-induced premature senescence in primary human keratinocytes.
Show in the study text Report a problemFND-2251471003
04LabIn vitro (cells)Mechanism
In primary human keratinocytes, AICAR diminished the increase in p53 transactivation.
In plain wordsIn cells, AICAR reduced the increase in p53 transactivation compared with H2O2 alone.
Peptide
AICAR (acadesine)
Outcome
Decreasep53 transactivation
Study
humann: not reported in source
primary human keratinocytes challenged with H2O2
Comparator
H2O2 without AICAR
Outcome group
Aging markers · Skin and wound
Studied dose
Dose not stated
Source sentences
Summary
In addition, AICAR diminished the increase in p53 transactivation.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of AMPK on H(2)O(2)-induced premature senescence in primary human keratinocytes.
Show in the study text Report a problemFND-2251471004

Studies that did not test the peptide alone1

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).

05LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In keratinocytes, Compound C, DN-AMPK expression or AMPK knockdown prevented the reduction in SA-Gal induced by AICAR.
In plain wordsIn cells, AMPK inhibition or genetic suppression prevented the reduction in SA-Gal induced by AICAR.
Peptide
AICAR (acadesine)
Outcome
Not applicableAMPK dependence of SA-Gal reduction
Study
humann: not reported in source
primary human keratinocytes challenged with H2O2
Outcome group
Aging markers · Skin and wound
Source sentences
Summary
The decreases in SA-Gal expression induced by resveratrol and AICAR were prevented by the pharmacological AMPK inhibitor Compound C, expression of a DN-AMPK or AMPK knock-down with shRNA.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of AMPK on H(2)O(2)-induced premature senescence in primary human keratinocytes.
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-2251471005

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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