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Effects of ischemia on skeletal muscle energy metabolism in mice lacking creatine kinase monitored by in vivo 31P nuclear magnetic resonance spectroscopy

in 't Zandt, H J LU ; Oerlemans, F; Wieringa, B and Heerschap, Arend (1999) In NMR in Biomedicine 12(6). p.34-327
Abstract

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... (More)

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).

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Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Adenosine Triphosphate, Animals, Creatine Kinase, Energy Metabolism, Female, Glycogen, Glycolysis, Ischemia, Isoenzymes, Lactates, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal, Nuclear Magnetic Resonance, Biomolecular, Oxidative Phosphorylation, Journal Article, Research Support, Non-U.S. Gov't
in
NMR in Biomedicine
volume
12
issue
6
pages
8 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:0032873143
ISSN
0952-3480
DOI
10.1002/(SICI)1099-1492(199910)12:6<327::AID-NBM570>3.0.CO;2-9
language
English
LU publication?
no
id
6235c558-6a14-4f5a-a2ba-731791c93da1
date added to LUP
2017-03-06 16:42:00
date last changed
2017-05-18 14:33:28
@article{6235c558-6a14-4f5a-a2ba-731791c93da1,
  abstract     = {<p>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).</p>},
  author       = {in 't Zandt, H J and Oerlemans, F and Wieringa, B and Heerschap, Arend},
  issn         = {0952-3480},
  keyword      = {Adenosine Triphosphate,Animals,Creatine Kinase,Energy Metabolism,Female,Glycogen,Glycolysis,Ischemia,Isoenzymes,Lactates,Male,Mice,Mice, Inbred C57BL,Mice, Knockout,Muscle, Skeletal,Nuclear Magnetic Resonance, Biomolecular,Oxidative Phosphorylation,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {6},
  pages        = {34--327},
  publisher    = {John Wiley & Sons},
  series       = {NMR in Biomedicine},
  title        = {Effects of ischemia on skeletal muscle energy metabolism in mice lacking creatine kinase monitored by in vivo 31P nuclear magnetic resonance spectroscopy},
  url          = {http://dx.doi.org/10.1002/(SICI)1099-1492(199910)12:6<327::AID-NBM570>3.0.CO;2-9},
  volume       = {12},
  year         = {1999},
}