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.

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

Effect of Soil Salinity on the Expression of Betaine Aldehyde Dehydrogenase in Leaves: Investigation of Hydraulic, Ionic and Biochemical Signals.

1992 ◽  
Vol 19 (5) ◽  
pp. 555 ◽  
Author(s):  
KF Mccue ◽  
AD Hanson
Keyword(s):  
Enzyme Activity ◽  
Aldehyde Dehydrogenase ◽  
Half Life ◽  
Mrna Level ◽  
State Level ◽  
Betaine Aldehyde Dehydrogenase ◽  
Mrna Levels ◽  
Betaine Aldehyde ◽  
Hydraulic Signal ◽  
Leaf Disks

Betaine aldehyde dehydrogenase (BADH) catalyses the last step in glycine betaine synthesis. The levels of BADH enzyme and BADH mRNA have previously been shown to be increased several-fold by salt stress. To characterise this induction more thoroughly, BADH mRNA levels and enzyme activities were analysed in leaves of sugar beet plants (Beta vulgaris L.) subjected to different salinisation regimes. Following a salt shock (transfer from 0 to 400 mM NaCI) BADH enzyme activity rose slowly for several days. In contrast, BADH mRNA level first decreased for several hours, and then increased. When salt was leached from the rooting medium of salinised plants, BADH enzyme activity declined, with a half-life of more than 4 days. However, the level of BADH mRNA declined sharply with an apparent half-life of 2 h showing that transcription of the BADH gene or the stability of BADH mRNA in leaves can respond very dynamically to salinity changes around the root. In plants which had been gradually salinised and then held at various NaCl concentrations, the steady state level of enzyme rose continuously between 0 and 500 mM NaCl, whereas that of BADH mRNA reached a plateau at 100 mM NaCl. In general, the observed BADH mRNA fluctuations could not be satisfactorily explained by assuming them to be responses to hydraulic signals. This suggests the participation of a non-hydraulic signal or signals coming from the root. The non-hydraulic signal is unlikely to be NaCl, because leaf disks exposed to salt concentrations typical of the apoplast of salinised leaves did not accumulate BADH mRNA. A biochemical messenger is thus implied. Although abscisic acid application to leaf disks elicited significant increases in BADH mRNA level, these were several-fold smaller than those observed in leaves of intact salinised plants, suggesting the involvement of some other substance.

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.

Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium

1997 ◽  
Vol 273 (1) ◽  
pp. H418-H425 ◽  
Author(s):  
T. Tsukube ◽  
J. D. McCully ◽  
K. R. Metz ◽  
C. U. Cook ◽  
S. Levitsky
Keyword(s):  
Functional Recovery ◽  
Cytosolic Calcium ◽  
High Energy ◽  
Left Ventricular ◽  
Global Ischemia ◽  
Nucleoside Triphosphate ◽  
Mrna Levels ◽  
High Energy Phosphates ◽  
Surgically Induced ◽  
Free Magnesium

Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, 31P nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded PCr depletion (P <0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mgf during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+]i accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.

OXIDATIVE DEFENSE ENZYME ACTIVITY AND mRNA LEVELS IN LENSES OF DIABETIC RATS

1997 ◽  
Vol 51 (6) ◽  
pp. 541-555 ◽  
Author(s):  
Peeyush Khanna ◽  
Lifei Wang ◽  
Regino J. Perez-Polo ◽  
Naseem H. Ansari
Keyword(s):  
Enzyme Activity ◽  
Diabetic Rats ◽  
Mrna Levels ◽  
Oxidative Defense ◽  
Defense Enzyme

scholarly journals Gene expression of the three members of hepatocyte nuclear factor-3 is differentially regulated by nutritional and hormonal factors

2000 ◽  
Vol 167 (1) ◽  
pp. R1-R5 ◽  
Author(s):  
M Imae ◽  
Y Inoue ◽  
Z Fu ◽  
H Kato ◽  
T Noguchi
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Regulation Of Gene Expression ◽  
Diabetic Rats ◽  
Physiological Status ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Protein Free Diet

Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). It has been shown that HNF-3 regulates a number of metabolically important genes. However, the mechanisms underlying this regulation of HNF-3 activity by hormones and nutrition have not yet been well elucidated. In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. Male Wistar rats were fed on a 12% casein diet, 12% gluten diet (deficient in lysine and threonine) or a protein-free diet for 1 week. The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). Insulin replacement in the diabetic rats decreased both mRNA levels in a dose-dependent manner. HNF-3alpha mRNA was not affected by insulin status. These results show that the genes of the three members of the HNF-3 family respond differently to hormonal and nutritional factors suggesting that the activities of HNF-3 members are regulated, at least in part, by the levels of their gene expression.

Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice

2001 ◽  
Vol 281 (3) ◽  
pp. E619-E625 ◽  
Author(s):  
M. Gorselink ◽  
M. R. Drost ◽  
W. A. Coumans ◽  
G. P. J. van Kranenburg ◽  
R. P. Hesselink ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Adenylate Kinase ◽  
Adenine Nucleotide ◽  
Recovery Period ◽  
High Energy ◽  
Wild Type ◽  
The Impact ◽  
Kinase Pathway ◽  
Contractile Performance ◽  
Atp Regeneration

Creatine kinase (CK) forms a small family of isoenzymes playing an important role in maintaining the concentration of ATP and ADP in muscle cells. To delineate the impact of a lack of CK activity, we studied contractile performance during a single maximal tetanic contraction and during 12 repeated tetanic contractions of intact dorsal flexors of CK knockout (CK−/−) mice. To investigate the effect on ATP regeneration, muscular high-energy phosphate content was determined at rest, immediately after the contraction series, and after a 60-s recovery period. Maximal torque of the dorsal flexors was significantly lower in CK−/− mice than in wild-type animals, i.e., 23.7 ± 5.1 and 33.3 ± 6.8 mN · m · g−1 wet wt, respectively. Lower muscle ATP (20.1 ± 1.4 in CK−/− vs. 28.0 ± 2.1 μmol/g dry wt in controls) and higher IMP (1.2 ± 0.5 in CK−/− vs. 0.3 ± 0.1 μmol/g dry wt in controls) levels at the onset of contraction may contribute to the declined contractility in CK−/− mice. In contrast to wild-type muscles, ATP levels could not be maintained during the series of 12 tetanic contractions of dorsal flexors of CK−/− mice and dropped to 15.5 ± 2.4 μmol/g dry wt. The significant increase in tissue IMP (2.4 ± 1.1 μmol/g dry wt) content after the contraction series indicates that ATP regeneration through adenylate kinase was not capable of fully compensating for the lack of CK. ATP regeneration via the adenylate kinase pathway is a likely cause of reduced basal adenine nucleotide levels in CK−/− mice.

scholarly journals Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

1988 ◽  
Vol 255 (3) ◽  
pp. E397-E402 ◽  
Author(s):  
S. R. Max ◽  
J. Mill ◽  
K. Mearow ◽  
M. Konagaya ◽  
Y. Konagaya ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Skeletal Muscles ◽  
Northern Blot Analysis ◽  
Mrna Level ◽  
Synthetase Activity ◽  
Mrna Levels ◽  
Glutamine Synthetase Activity ◽  
Global Response ◽  
Tubulin Mrna ◽  
Major Increase

The regulation of glutamine synthetase expression by dexamethasone was studied in rat skeletal muscles. Daily administration of dexamethasone caused striking enhancement of glutamine synthetase activity in plantaris, soleus, and diaphragm muscles. Northern blot analysis revealed that the dexamethasone-mediated increase of glutamine synthetase activity was associated with dramatically increased levels of glutamine synthetase mRNA. Both glutamine synthetase activity and mRNA levels were significantly elevated in plantaris muscle at 0.5 mg.kg-1.day-1 of dexamethasone, a dose that approximates endogenous corticosteroid levels in animals under severe stress. Quantification of changes in glutamine synthetase mRNA on the basis of total mRNA (by oligo dT hybridization) also revealed a major increase in glutamine synthetase mRNA. Dexamethasone was without effect on beta-tubulin mRNA levels, indicating that glutamine synthetase induction is not part of a global response to glucocorticoids. Dexamethasone treatment resulted in only an approximately 15% increase in glutamine synthetase activity in heart; there was no change in glutamine synthetase mRNA level in this tissue. Thus glucocorticoids regulate glutamine synthetase gene expression in rat skeletal muscles.

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