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Exposure to Hydrogen Peroxide Induces Oxidation and Activation of AMP-activated Protein Kinase
- Publication Year :
- 2010
- Publisher :
- The University of North Carolina at Chapel Hill University Libraries, 2010.
-
Abstract
- 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.
- Subjects :
- Oxidative phosphorylation
AMP-Activated Protein Kinases
Biochemistry
Cell Line
Acatalasia
Mice
chemistry.chemical_compound
Adenosine Triphosphate
AMP-activated protein kinase
Catalytic Domain
Animals
Humans
Enzyme Inhibitors
Kinase activity
Protein kinase A
Molecular Biology
Amitrole
biology
Kinase
AMPK
Hydrogen Peroxide
Cell Biology
Catalase
Oxidants
Glutathione
Adenosine Monophosphate
Cell biology
chemistry
Enzyme Induction
Mutation
biology.protein
Oxidation-Reduction
Protein Processing, Post-Translational
Adenosine triphosphate
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....535330649eb71117f9fc9371a3e59c1b
- Full Text :
- https://doi.org/10.17615/8drv-9917