Effects of ischemia on skeletal muscle energy metabolism in mice lacking creatine kinase monitored by in vivo P-31 nuclear magnetic resonance spectroscopy
| Autor: | Arend Heerschap, Frank Oerlemans, B. Wieringa, H J A in 't Zandt |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Adaptation and Cell Death [Cellular reprogramming in tissues of neuro-muscular origin as a response on genetic defects in the network for energy-homeostasis] Glycogen Wild type Skeletal muscle Oxidative phosphorylation Biology adaptatie en celdood [Cellulaire herprogrammering in neuromusculaire weefsels in respons op genetische defecten in het cellulaire netwerk voor energie-homeostase] Phosphocreatine chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry In vivo Internal medicine biology.protein medicine Molecular Medicine Radiology Nuclear Medicine and imaging Creatine kinase Glycolysis NMR van skeletspieren NMR of skeletal muscle Spectroscopy |
| Zdroj: | NMR in Biomedicine, 12, 327-334 NMR in Biomedicine, 12, 6, pp. 327-334 |
| ISSN: | 0952-3480 |
| Popis: | The aim of this study was to provide in vivo experimental evidence for the proposed biological significance of the creatine kinase (CK)/phosphocreatine (PCr) system in the energy metabolism of skeletal muscle. As a test system we compared hindlimb muscle of knockout mice lacking the cytosolic M-type (M-CK(-)/(-)), the mitochondrial ScMit-type (ScCKmit(-)/(-)), or both creatine kinase isoenzymes (CK(-)/(-)), and in vivo 31P-NMR was used to monitor metabolic responses during and after an ischemic period. Although single mutants show some subtle specific abnormalities, in general their metabolic responses appear similar to wild type, in contrast to CK(-)/(-) double mutants. This implies that presence of one CK isoform is both necessary and sufficient for the system to be functional in meeting ischemic stress conditions. The global ATP buffering role of the CK/PCr system became apparent in a 30% decline of ATP in the CK(-)/(-) mice during ischemia. Both M-CK(-)/(-) and CK(-)/(-) showed increased phosphomonoester levels during ischemia, most likely reflecting adaptation to a more efficient utilization of glycogenolysis. While in M-CK(-)/(-) muscle PCr can still be hydrolyzed to provide Pi for this process, in CK(-)/(-) muscle only Pi from ATP breakdown is available and Pi levels increase much more slowly. The experiments also revealed that the system plays a role in maintaining pH levels; the CK(-)/(-) mice showed a faster and more pronounced acidification (pH = 6.6) than muscles of wild type and single knockout mutants (pH = 6.9). |
| Databáze: | OpenAIRE |
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