Bundgaard 2019 Sci Rep

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Bundgaard A, James AM, Gruszczyk AV, Martin J, Murphy MP, Fago A (2019) Metabolic adaptations during extreme anoxia in the turtle heart and their implications for ischemia-reperfusion injury. Sci Rep 9:2850.

» PMID: 30808950 Open Access

Bundgaard A, James AM, Gruszczyk AV, Martin J, Murphy MP, Fago A (2019) Sci Rep

Abstract: ATP depletion and succinate accumulation during ischemia lead to oxidative damage to mammalian organs upon reperfusion. In contrast, freshwater turtles survive weeks of anoxia at low temperatures without suffering from oxidative damage upon reoxygenation, but the mechanisms are unclear. To determine how turtles survive prolonged anoxia, we measured ~80 metabolites in hearts from cold-acclimated (5 °C) turtles exposed to 9 days anoxia and compared the results with those for normoxic turtles (25 °C) and mouse hearts exposed to 30 min of ischemia. In turtles, ATP and ADP decreased to new steady-state levels during fasting and cold-acclimation and further with anoxia, but disappeared within 30 min of ischemia in mouse hearts. High NADH/NAD+ ratios were associated with succinate accumulation in both anoxic turtles and ischemic mouse hearts. However, succinate concentrations and succinate/fumarate ratios were lower in turtle than in mouse heart, limiting the driving force for production of reactive oxygen species (ROS) upon reoxygenation in turtles. Furthermore, we show production of ROS from succinate is prevented by re-synthesis of ATP from ADP. Thus, maintenance of an ATP/ADP pool and low succinate accumulation likely protects turtle hearts from anoxia/reoxygenation injury and suggests metabolic interventions as a therapeutic approach to limit ischemia/reperfusion injury in mammals.


Bioblast editor: Plangger M


Labels: MiParea: Respiration, Comparative MiP;environmental MiP 

Stress:Ischemia-reperfusion, Oxidative stress;RONS  Organism: Mouse, Reptiles  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Regulation: ADP  Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k, O2k-Fluorometer 

2019-03, Amplex UltraRed