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Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase
Open accessAbstract
Although metabolic conditions associated with an increased AMP/ATP ratio are primary factors in the activation of 5'-adenosine monophosphate-activated protein kinase (AMPK), a number of recent studies have shown that increased intracellular levels of reactive oxygen species can stimulate AMPK activity, even without a decrease in cellular levels of ATP. We found that exposure of recombinant AMPKαβγ complex or HEK 293 cells to H(2)O(2) was associated with increased kinase activity and also resulted in oxidative modification of AMPK, including S-glutathionylation of the AMPKα and AMPKβ subunits. In experiments using C-terminal truncation mutants of AMPKα (amino acids 1-312), we found that mutation of cysteine 299 to alanine diminished the ability of H(2)O(2) to induce kinase activation, and mutation of cysteine 304 to alanine totally abrogated the enhancing effect of H(2)O(2) on kinase activity. Similar to the results obtained with H(2)O(2)-treated HEK 293 cells, activation and S-glutathionylation of the AMPKα subunit were present in the lungs of acatalasemic mice or mice treated with the catalase inhibitor aminotriazole, conditions in which intracellular steady state levels of H(2)O(2) are increased. These results demonstrate that physiologically relevant concentrations of H(2)O(2) can activate AMPK through oxidative modification of the AMPKα subunit. The present findings also imply that AMPK activation, in addition to being a response to alterations in intracellular metabolic pathways, is directly influenced by cellular redox status.
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“Recent lines of evidence have demonstrated AMPK responsiveness to imbalanced redox status, thus bringing new insights into the networks of redox-stimulated signals upstream of AMPK (Table 1) [42,43,44,45,46,47,48,49,50,51].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [48]
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“Exogenous or glucose oxidase-generated hydrogen peroxide induced direct S-glutathionylation on the AMPKα subunit at Cys299 and Cys304, which contributes to AMPK activation [48].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [48]
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Management of cellular energy by the AMP‐activated protein kinase system
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Metadata
- Authors
- Zmijewski, J. W., Banerjee, S., Bae, H., Friggeri, A., Lazarowski, E. R., & Abraham, E.
- Affiliations
- University of Alabama at Birmingham (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Zmijewski, Jaroslaw W.
- Abraham, Edward
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 285
- Issue
- 43
- Pages
- 33154-33164
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2963401
- OpenAlex
- W2073966685
- Cited by
- 441
- References
- 68
- Citations by year
- 2026: 21 · 2025: 35 · 2024: 30 · 2023: 22 · 2022: 41 · 2021: 40 · 2020: 45 · 2019: 28 · 2018: 27 · 2017: 27 · 2016: 26 · 2015: 30 · 2014: 22 · 2013: 22 · 2012: 15
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-62221, P01HL034322, HL 76206, R01HL076206, R01HL062221)
- National Institute of General Medical Sciences (R01GM087748, GM87748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- AMPK, hydrogen peroxide, oxidative modification, S-glutathionylation, reactive oxygen species, cysteine residues, redox state, catalase inhibition, 3-amino-1,2,4-triazole, AMP/ATP ratio, kinase activation
- MeSH terms
- Adenosine Monophosphate, Adenosine Triphosphate, Amitrole, Animals, Catalase, Cell Line, Enzyme Induction, Enzyme Inhibitors, Glutathione, Humans, Hydrogen Peroxide, Mutation, Oxidation-Reduction, Protein Processing, Post-Translational, Oxidants, Catalytic Domain, Acatalasia, Mice, AMP-Activated Protein Kinases
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