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Mitochondrial creatine kinase activity and phosphate shuttling are acutely regulated by exercise in human skeletal muscle.
Perry CG, Kane DA, Herbst EA, Mukai K, Lark DS, Wright DC, Heigenhauser GJ, Neufer PD, Spriet LL, Holloway GP
(2012) J Physiol 590: 5475-86
MeSH Terms: Adenosine Diphosphate, Animals, Creatine Kinase, Mitochondrial Form, Exercise, Humans, Male, Muscle Contraction, Muscle, Skeletal, Rats, Rats, Sprague-Dawley
Show Abstract · Added January 23, 2015
Energy transfer between mitochondrial and cytosolic compartments is predominantly achieved by creatine-dependent phosphate shuttling (PCr/Cr) involving mitochondrial creatine kinase (miCK). However, ADP/ATP diffusion through adenine nucleotide translocase (ANT) and voltage-dependent anion carriers (VDACs) is also involved in this process. To determine if exercise alters the regulation of this system, ADP-stimulated mitochondrial respiratory kinetics were assessed in permeabilized muscle fibre bundles (PmFBs) taken from biopsies before and after 2 h of cycling exercise (60% ) in nine lean males. Concentrations of creatine (Cr) and phosphocreatine (PCr) as well as the contractile state of PmFBs were manipulated in situ. In the absence of contractile signals (relaxed PmFBs) and miCK activity (no Cr), post-exercise respiratory sensitivity to ADP was reduced in situ (up to 126% higher apparent K(m) to ADP) suggesting inhibition of ADP/ATP diffusion between matrix and cytosolic compartments (possibly ANT and VDACs). However this effect was masked in the presence of saturating Cr (no effect of exercise on ADP sensitivity). Given that the role of ANT is thought to be independent of Cr, these findings suggest ADP/ATP, but not PCr/Cr, cycling through the outer mitochondrial membrane (VDACs) may be attenuated in resting muscle after exercise. In contrast, in contracted PmFBs, post-exercise respiratory sensitivity to ADP increased with miCK activation (saturating Cr; 33% lower apparent K(m) to ADP), suggesting prior exercise increases miCK sensitivity in situ. These observations demonstrate that exercise increases miCK-dependent respiratory sensitivity to ADP, promoting mitochondrial-cytosolic energy exchange via PCr/Cr cycling, possibly through VDACs. This effect may mask an underlying inhibition of Cr-independent ADP/ATP diffusion. This enhanced regulation of miCK-dependent phosphate shuttling may improve energy homeostasis through more efficient coupling of oxidative phosphorylation to perturbations in cellular energy charge during subsequent bouts of contraction.
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10 MeSH Terms
Increased activity of serum mitochondrial isoenzyme of creatine kinase in hepatocellular carcinoma patients predominantly with recurrence.
Soroida Y, Ohkawa R, Nakagawa H, Satoh Y, Yoshida H, Kinoshita H, Tateishi R, Masuzaki R, Enooku K, Shiina S, Sato T, Obi S, Hoshino T, Nagatomo R, Okubo S, Yokota H, Koike K, Yatomi Y, Ikeda H
(2012) J Hepatol 57: 330-6
MeSH Terms: Aged, Biomarkers, Carcinoma, Hepatocellular, Creatine Kinase, Mitochondrial Form, Female, Humans, Isoenzymes, Liver Neoplasms, Male, Middle Aged, Neoplasm Recurrence, Local, Protein Precursors, Prothrombin, RNA, Messenger, alpha-Fetoproteins
Show Abstract · Added May 2, 2014
BACKGROUND & AIMS - Mitochondrial isoenzyme of creatine kinase (MtCK) is reportedly highly expressed in hepatocellular carcinoma (HCC). Clinical relevance of serum MtCK activity in patients with HCC was assessed using a novel immuno-inhibition method.
METHODS - Among patients with cirrhosis caused by hepatitis B or C virus, 147 patients with HCC (12 with the first occurrence and 135 with recurrence) and 92 patients without HCC were enrolled.
RESULTS - Serum MtCK activity was higher in cirrhotic patients with HCC than in those without HCC or healthy subjects. Elevated serum MtCK activity in HCC patients decreased after radiofrequency ablation. In case of prediction of HCC, MtCK had a sensitivity of 62.6% and a specificity of 70.7% at a cut-off point of 8.0 U/L, with an area under the receiver operating curve of 0.722 vs. 0.713 for alpha-fetoprotein (AFP) and 0.764 for des-gamma-carboxy prothrombin (DCP). Among the HCC patients, serum MtCK activity was elevated in 52.9% individuals with serum AFP level < 20 ng/ml and 63.2% individuals with serum DCP level < 40 mAu/ml. Even in patients with a single HCC ≤ 2 cm, the sensitivity of serum MtCK activity for the prediction of HCC was 64.4%, which was comparable to the overall sensitivity. This increased activity was due to an increase in ubiquitous MtCK, not sarcomeric MtCK, and the enhanced mRNA expression of ubiquitous MtCK was observed in cell lines originating from HCCs in contrast to healthy liver tissues.
CONCLUSIONS - Serum MtCK activity merits consideration as a novel marker for HCC to be further tested as for its diagnostic and prognostic power.
Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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15 MeSH Terms