BioAcyl Corp |
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| Resource type: Journal Article DOI: 10.1074/jbc.M104425200 ID no. (ISBN etc.): 0021-9258 BibTeX citation key: Pucar2001 View all bibliographic details |
Categories: BioAcyl Corp Subcategories: Stress resistant phenotype Creators: Bast, Dzeja, others, Pucar Collection: Journal of Biological Chemistry |
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| Abstract |
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Cell survival is critically dependent on the preservation of cellular bioenergetics. However, the metabolic mechanisms that confer resistance to injury are poorly understood. Phosphotransfer reactions integrate ATP-consuming with ATP-producing processes and could thereby contribute to the generation of a protective phenotype. Here, we used ischemic preconditioning to induce a stress-tolerant state and 18O-assisted31P nuclear magnetic resonance spectroscopy to capture intracellular phosphotransfer dynamics. Preconditioning of isolated perfused hearts triggered a redistribution in phosphotransfer flux with significant increase in creatine kinase and glycolytic rates. High energy phosphoryl fluxes through creatine kinase, adenylate kinase, and glycolysis in preconditioned hearts correlated tightly with post-ischemic functional recovery. This was associated with enhanced metabolite exchange between subcellular compartments, manifested by augmented transfer of inorganic phosphate from cellular ATPases to mitochondrial ATP synthase. Preconditioning-induced energetic remodeling protected cellular ATP synthesis and ATP consumption, improving contractile performance following ischemia-reperfusion insult. Thus, the plasticity of phosphotransfer networks contributes to the effective functioning of the cellular energetic system, providing a mechanism for increased tolerance toward injury.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |