Cell survival during
hypoxia exposure requires a metabolic reorganization to decrease
ATP demands to match the reduced capacity for
ATP production. We investigated whether
AMP-activated protein kinase (AMPK) activity responds to 12 h exposure to severe
hypoxia ( approximately 0.3 mg O2 l(-1)) in the
anoxia-tolerant goldfish (Carassius auratus).
Hypoxia exposure in goldfish was characterized by a strong activation of
creatine phosphate hydrolysis and glycolysis in liver and muscle. AMPK activity increased by approximately 5.5-fold in goldfish liver within 0.5 h
hypoxia exposure and this increase in activity was temporally associated with an 11-fold increase in [
AMP(free)]/[
ATP]. No changes in total AMPK
protein amount were observed, suggesting that the changes in AMPK activity are due to post-translational phosphorylation of the
protein.
Hypoxia exposure had no effect on the expression of two identified AMPK alpha-subunit
isoforms and caused an approximately 50% decrease in the
mRNA levels of AMPK beta-subunit
isoform. Changes in AMPK activity in the liver were associated with an increase in percentage phosphorylation of a well-characterized target of AMPK, eukaryotic elongation factor-2 (eEF2), and decreases in
protein synthesis rates measured in liver cell-free extracts. No activation of AMPK was observed in muscle, brain, heart or gill during the 12 h
hypoxia exposure suggesting a tissue-specific regulation of AMPK possibly related to a lack of change in cellular [
AMP(free)]/[
ATP] as observed in muscle.