Influence of mitochondrial creatine kinase on the mitochondrial/extramitochondrial distribution of high energy phosphates in muscle tissue: evidence for a leak in the creatine shuttle

1994 ◽  
Vol 133-134 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Sibylle Soboll ◽  
Annette Conrad ◽  
Siegbert Hebisch
Keyword(s):  
Creatine Kinase ◽  
Muscle Tissue ◽  
High Energy ◽  
High Energy Phosphates ◽  
Mitochondrial Creatine Kinase

Carbofuran-induced alterations (in vivo) in high-energy phosphates, creatine kinase (CK) and CK isoenzymes

1991 ◽  
Vol 65 (4) ◽  
pp. 304-310 ◽  
Author(s):  
Ramesh C. Gupta ◽  
John T. Goad ◽  
Wade L. Kadel
Keyword(s):  
Creatine Kinase ◽  
High Energy ◽  
High Energy Phosphates

Cardiac force and high-energy phosphates under metabolic inhibition in four ectothermic vertebrates

1996 ◽  
Vol 271 (4) ◽  
pp. R946-R954 ◽  
Author(s):  
T. Hartmund ◽  
H. Gesser
Keyword(s):  
Creatine Kinase ◽  
Atpase Activity ◽  
Kinase Activity ◽  
Energy State ◽  
High Energy ◽  
Creatine Kinase Activity ◽  
The Other ◽  
Freshwater Turtle ◽  
High Energy Phosphates ◽  
Isometric Twitch

Isometric twitch tension of ventricular preparations stimulated at 0.2 Hz fell over 30 min of anoxia by a fraction decreasing in the order rainbow trout, cod, eel, and freshwater turtle. Drops in the estimated cytoplasmic energy state were related to larger tension losses for trout than for the other species, possibly due to larger changes in free phosphate. Anoxic energy degradation was slower for turtle than for the other species. Anoxia combined with glycolytic inhibition (1 mmol/l iodoacetate) enhanced the decrease in twitch tension for a drop in energy state and enlarged the increase in ADP/ATP relative to that in creatine/phosphocreatine to an extent inversely related to the creatine kinase activity. Furthermore, it increased resting tension to an extent possibly related to myosin-adenosinetriphosphatase (ATPase) activity and lowered the content of phosphorylated adenylates in trout and turtle myocardium. The results indicate that species differences in performance of the metabolically challenged myocardium depend on energy-degrading processes, e.g., myosin-ATPase activity, phosphate release, creatine kinase activity, and efflux/degradation of ADP and AMP, and that glycolysis offers protection due to its cytoplasmic localization.

scholarly journals Niacin protects the isolated heart from ischemia-reperfusion injury

2000 ◽  
Vol 279 (2) ◽  
pp. H764-H771 ◽  
Author(s):  
Nathan A. Trueblood ◽  
Ravichandran Ramasamy ◽  
Li Feng Wang ◽  
Saul Schaefer
Keyword(s):  
Creatine Kinase ◽  
Redox Regulation ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
High Energy ◽  
Low Flow ◽  
High Energy Phosphates ◽  
Zero Flow ◽  
Pyruvate Ratio

Nicotinic acid (niacin) has been shown to decrease myocyte injury. Because interventions that lower the cytosolic NADH/NAD+ratio improve glycolysis and limit infarct size, we hypothesized that 1) niacin, as a precursor of NAD+, would lower the NADH/NAD+ratio, increase glycolysis, and limit ischemic injury and 2) these cardioprotective benefits of niacin would be limited in conditions that block lactate removal. Isolated rat hearts were perfused without (Ctl) or with 1 μM niacin (Nia) and subjected to 30 min of low-flow ischemia (10% of baseline flow, LF) and reperfusion. To examine the effects of limiting lactate efflux, experiments were performed with 1) Ctl and Nia groups subjected to zero-flow ischemia and 2) the Nia group treated with the lactate-H+cotransport inhibitor α-cyano-4-hydroxycinnamate under LF conditions. Measured variables included ATP, pH, cardiac function, tissue lactate-to-pyruvate ratio (reflecting NADH/NAD+), lactate efflux rate, and creatine kinase release. The lactate-to-pyruvate ratio was reduced by more than twofold in Nia-LF hearts during baseline and ischemic conditions ( P < 0.001 and P< 0.01, respectively), with concurrent lower creatine kinase release than Ctl hearts ( P < 0.05). Nia-LF hearts had significantly greater lactate release during ischemia ( P < 0.05 vs. Ctl hearts) as well as higher functional recovery and a relative preservation of high-energy phosphates. Inhibiting lactate efflux with α-cyano-4-hydroxycinnamate and blocking lactate washout with zero flow negated some of the beneficial effects of niacin. During LF, niacin lowered the cytosolic redox state and increased lactate efflux, consistent with redox regulation of glycolysis. Niacin significantly improved functional and metabolic parameters under these conditions, providing additional rationale for use of niacin as a therapeutic agent in patients with ischemic heart disease.

Contractile and metabolic effects of increased creatine kinase activity in mouse skeletal muscle

1996 ◽  
Vol 270 (4) ◽  
pp. C1236-C1245 ◽  
Author(s):  
B. B. Roman ◽  
J. M. Foley ◽  
R. A. Meyer ◽  
A. P. Koretsky
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Kinase Activity ◽  
Contractile Function ◽  
Contractile Activity ◽  
High Energy ◽  
Metabolic Effects ◽  
High Energy Phosphates ◽  
Lactate Dehydrogenase Activity ◽  
B Subunit

The effects of increased expression of creatine kinase (CK) in skeletal muscle were studied in control and transgenic animals homozygous for expression of the B subunit of CK. CK activity was 47% higher in transgenic gastrocnemius muscle. The CK activity was distributed as follows: 45 +/- 1% MM dinner, 31 +/- 4% MB dimer, and 22 +/- 5% BB dimer. No significant differences in metabolic or contractile proteins were detected except for a 22% decrease in lactate dehydrogenase activity and a 9% decrease in adenylate kinase activity. The only significant effect in contractile activity was that the rise time of a 5-s isometric contraction was 28% faster in the transgenic muscle. 31P nuclear magnetic resonance (NMR) spectra were obtained from control and transgenic muscles during mechanical activation, and there were no NMR measurable differences detected. These results indicate that a 50% increase in CK activity due to expression of the B subunit does not have large effects on skeletal muscle metabolism or contractile function. Therefore, control muscle has sufficient CK activity to keep up with changes in cellular high-energy phosphates except during the early phase of intense contractile activity.

scholarly journals Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

1997 ◽  
Vol 82 (5) ◽  
pp. 1416-1423 ◽  
Author(s):  
Jon F. Watchko ◽  
Monica J. Daood ◽  
Gary C. Sieck ◽  
John J. Labella ◽  
Bill T. Ameredes ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
High Energy ◽  
Maximum Power ◽  
Absolute Maximum ◽  
Work Output ◽  
Mitochondrial Creatine Kinase ◽  
Tetanic Force ◽  
Mouse Diaphragm ◽  
Dynamic Contractions ◽  
Isotonic Function

Watchko, Jon F., Monica J. Daood, Gary C. Sieck, John J. LaBella, Bill T. Ameredes, Alan P. Koretsky, and Be Wieringa. Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function. J. Appl. Physiol. 82(5): 1416–1423, 1997.—Creatine kinase (CK) is an enzyme central to cellular high-energy phosphate metabolism in muscle. To characterize the physiological role of CK in respiratory muscle during dynamic contractions, we compared the force-velocity relationships, power, and work output characteristics of the diaphragm (Dia) from mice with combined myofibrillar and sarcomeric mitochondrial CK deficiency (CK[−/−]) with CK-sufficient controls (Ctl). Maximum velocity of shortening was significantly lower in CK[−/−] Dia (14.1 ± 0.9 L o/s, where L o is optimal fiber length) compared with Ctl Dia (17.5 ± 1.1 L o/s) ( P < 0.01). Maximum power was obtained at 0.4–0.5 tetanic force in both groups; absolute maximum power (2,293 ± 138 W/m2) and work (201 ± 9 J/m2) were lower in CK[−/−] Dia compared with Ctl Dia (2,744 ± 146 W/m2 and 284 ± 26 J/m2, respectively) ( P < 0.05). The ability of CK[−/−] Dia to sustain shortening during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load) was markedly impaired, with CK[−/−] Dia power and work declining to zero by 37 ± 4 s, compared with 61 ± 5 s in Ctl Dia. We conclude that combined myofibrillar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work output, underscoring the functional importance of CK during dynamic contractions in skeletal muscle.

Diabetes decreases creatine kinase enzyme activity and mRNA level in the rat heart

1989 ◽  
Vol 257 (4) ◽  
pp. E573-E577 ◽  
Author(s):  
B. K. Popovich ◽  
K. R. Boheler ◽  
W. H. Dillmann
Keyword(s):  
Creatine Kinase ◽  
Enzyme Activity ◽  
Northern Blot Analysis ◽  
Mrna Level ◽  
Cdna Probe ◽  
High Energy ◽  
Diabetic Rats ◽  
Mrna Levels ◽  
High Energy Phosphates ◽  
Contractile Performance

Several of the adenosinetriphosphatase enzymes that are responsible for cardiac muscle contraction rely on high-energy phosphates supplied by the creatine kinase (CK) system. Experimental diabetes mellitus has been shown to cause a decrease in the maximal contractile performance of the heart. We postulated that the decrease in contractile performance may be explained in part by a decrease in CK enzyme activity. To evaluate this possibility, we determined the level of CK activity and isoenzyme distribution in ventricular homogenates from normal, diabetic, and insulin-treated diabetic rats. We found that total CK activity was decreased by 35% in diabetic hearts and that a 66% reduction in the cardiac-specific MB isoenzyme occurs. Using a cDNA probe for CK-muscle (M) RNA in Northern blot analysis, we determined that a 61.1% decrease in CK-M mRNA occurs in diabetes. Chronic insulin therapy for 1 mo restores CK-M mRNA levels and enzyme activity. In conclusion, diabetes-induced CK enzyme decreases are mediated in part by a lower level of CK-M mRNA that codes for the major CK-M subunit protein. Decreased performance of the CK system may contribute to diabetic cardiomyopathy.

scholarly journals Diaphragm and cardiac mitochondrial creatine kinases are impaired in sepsis

2007 ◽  
Vol 102 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Leigh A. Callahan ◽  
Gerald S. Supinski
Keyword(s):  
Creatine Kinase ◽  
Oxygen Consumption ◽  
Transport System ◽  
Phosphate Transport ◽  
High Energy ◽  
Creatine Kinase Activity ◽  
Functional Coupling ◽  
Mitochondrial Creatine Kinase ◽  
Western Blots ◽  
Protein Levels

Previous studies indicate that ATP formation by the electron transport chain is impaired in sepsis. However, it is not known whether sepsis affects the mitochondrial ATP transport system. We hypothesized that sepsis inactivates the mitochondrial creatine kinase (MtCK)-high energy phosphate transport system. To examine this issue, we assessed the effects of endotoxin administration on mitochondrial membrane-bound creatine kinase, an important trans-mitochondrial ATP transport system. Diaphragms and hearts were isolated from control ( n = 12) and endotoxin-treated (8 mg·kg−1·day−1; n = 13) rats after pentobarbital anesthesia. We isolated mitochondria using techniques that allow evaluation of the functional coupling of mitochondrial creatine kinase MtCK activity to oxidative phosphorylation. MtCK functional activity was established by 1) determining ATP/creatine-stimulated oxygen consumption and 2) assessing total creatine kinase activity in mitochondria using an enzyme-linked assay. We examined MtCK protein content using Western blots. Endotoxin markedly reduced diaphragm and cardiac MtCK activity, as determined both by ATP/creatine-stimulated oxygen consumption and by the enzyme-linked assay (e.g., ATP/creatine-stimulated mitochondrial respiration was 173.8 ± 7.3, 60.5 ± 9.3, 210.7 ± 18.9, was 67.9 ± 7.3 natoms O·min−1·mg−1 in diaphragm control, diaphragm septic, cardiac control, and cardiac septic samples, respectively; P < 0.001 for each tissue comparison). Endotoxin also reduced diaphragm and cardiac MtCK protein levels (e.g., protein levels declined by 39.5% in diaphragm mitochondria and by 44.2% in cardiac mitochondria; P < 0.001 and P = 0.009, respectively, comparing sepsis to control conditions). Our data indicate that endotoxin markedly impairs the MtCK-ATP transporter system; this phenomenon may have significant effects on diaphragm and cardiac function.

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