The role of AMP-activated protein kinase in the coordination of metabolic suppression in the common goldfish

• Main Author: Jibb, Lindsay A.
• Format: Others
• Language: English
• Published: University of British Columbia 2008
• Subjects: Hypoxia; Metabolism; Kinase; Goldfish; Oxygen deprivation
• Online Access: http://hdl.handle.net/2429/2504

Cell survival in conditions of severe oxygen deprivation depends on a wide variety of biochemical modifications, which result in a large-scale suppression of metabolism, preventing [ATP] from falling to fatally low levels. We investigated whether AMP-activated protein kinase (AMPK) has a role in the coordination of cellular modification during hypoxia, which leads to a regulated state of metabolic suppression in the goldfish (Carassius auratus). Energy charge, AMPK activity, protein and gene expression, as well as the translational capacity and phosphorylation state of a downstream target were measured in goldfish tissues during exposure to hypoxia (-0.3 mg 02/L) for up to 12 h. AMPK activity in the goldfish liver increased by 4-fold at 0.5 h hypoxia and was temporally associated with a —11-fold increase in calculated AMPfree/ATP. No change was observed in total AMPK protein or relative gene expression of identified AMPK isoforms. Changes in AMPK activity were also associated with a decreased rate of protein synthesis and an increase in the phosphorylated form of eukaryotic elongation factor-2 (eEF2; relative to total eEF2). Increases in AMPK activity were not seen in hypoxic goldfish muscle, brain, heart or gill, nor was a significant alteration in cellular energy charge seen in muscle. Still, the present study is the first to show that AMPK activity increases in liver in response to short-term severe hypoxia exposure in a hypoxia-tolerant fish. The decreased rates of protein synthesis, a well known component of metabolic suppression, combined with increased phosphorylation of eEF2, a downstream target of AMPK, potentially implicate the kinase in the cellular effort to suppress metabolism in hypoxia-tolerant species during oxygen deprivation. === Science, Faculty of === Zoology, Department of === Graduate