Journal
FEBS LETTERS
Volume 588, Issue 18, Pages 3361-3366Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2014.07.025
Keywords
AMP; ADP; AMP-activated protein kinase; Hydrogen peroxide; Oxidative stress
Funding
- Wellcome Trust [097726]
- AstraZeneca
- Boehringer-Ingel-heim
- GlaxoSmithKline
- Merck KgaA
- Janssen Pharmaceutica
- Pfizer
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AMPK is known to be activated by oxidative stress. Addition of glucose oxidase to cells generates H2O2 at a constant rate that is opposed by enzymic degradation, providing a good model for physiological oxidative stress. AMPK activation by glucose oxidase correlated with increases in cellular AMP:ATP and was greatly reduced in cells expressing an AMP-insensitive AMPK mutant, although a small degree of activation remained. The effects of increased AMP were partly due to inhibition of Thr172 dephosphorylation. These results suggest that changes in adenine nucleotides, rather than direct oxidative modification, are the major drivers of AMPK activation during oxidative stress. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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