PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Creatine Kinase, MM Form”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2001

[Creatine kinase and its isozymes].

Creatine kinase (CK; EC 2.7.3.2) is found in a variety of striated and smooth muscles, and the brain, and is an important enzyme regulator of high-energy phosphate production and utilization within contractile tissues. Serum CK activity is measured routinely as a sensitive indicator of injuries to the skeletal muscle and myocardium. CK has three isozymes (CK-MM, CK-MB and CK-BB) in cytoplasm and two isozymes (non-sarcomeric and sarcomeric) in mitochondria. CK isozymes provide more specific information about injured tissue because of their tissue distribution. CK-MM is useful in skeletal muscle diseases, such as muscle dystrophy, CK-MB in acute myocardial infarction (AMI), and CK-BB in brain damage and malignant tumor of the gastro-intestinal tract. CK-MB is measured either by enzyme activity or mass concentration and is measured as a marker not only in the diagnosis of AMI but also in suspected AMI and unstable angina. Mitochondrial CK, a useful indicator for pinpointing the severeness of muscle injuries, and CK-linked immunoglobulin are recognized as macro-CK because of their large molecular size.

Angina, Unstable↗
PubMed1984

Purification and characterization of naturally occurring and in vitro induced multiple forms of MM creatine kinase.

MM creatine kinase purified from tissue exists as a single form but upon release into the plasma exhibits three forms which, based on increasing anodal migration on polyacrylamide gel electrophoresis, are referred to as MM1, MM2, and MM3. The three forms were isolated in pure form from plasma in sufficient quantities for biochemical and physiological studies. Chromatofocusing results show that MM1, MM2, and MM3 have distinct isoelectric points of 7.58, 7.43, and 7.30, respectively. Analysis on high pressure liquid chromatography showed MM1 and tissue creatine kinase (MMt) to have identical peptide maps, but MM2 and MM3 were different in at least one amino acid. Tissue MM creatine kinase was converted in vitro to MM2 and MM3 after incubation in plasma. Conversion was unaffected by nonspecific proteases but inhibited by benzoylarginine, epsilon-amino caproic acid, and guanidinoethylmercaptosuccinic acid, specific inhibitors of carboxypeptidase N. Digestion of purified tissue MM creatine kinase with carboxypeptidases N and B produced MM2 and MM3 which were identical with the forms produced in vivo. Hybridization experiments with MM1 plus MM3 produced all three forms, as did tissue MM creatine kinase plus MM2. MM2 was also able to produce all three forms in the experiments. The plasma half-life of tissue MM creatine kinase or MM1 was shown to be about one-half that of MM3. The results suggest that hydrolytic cleavage of a basic amino acid, presumably by carboxypeptidase N, is responsible for conversion of MMt to MM2 and MM3. COOH-terminal amino acid analysis demonstrated the COOH-terminal amino acid of canine and rabbit MM1 to be lysine. Thus, we conclude that cleavage of the COOH-terminal lysine from MMt by serum carboxypeptidase N generates two additional MM creatine kinase isoforms with prolonged plasma clearance rates.

Animals↗
PubMed2004

A novel mechanism of regulation of cardiac contractility by mitochondrial functional state.

It is generally considered that mitochondria regulate cardiac cell contractility by providing ATP for cellular ATPases and by participating in Ca2+ homeostasis. However, other possible mechanisms by which mitochondria can influence contractility have been largely overlooked. Here, we demonstrate that inhibition of the mitochondrial electron transport chain strongly increases Ca2+-dependent and independent isometric force development in rat ventricular fibers with selectively permeabilized sarcolemma. This effect is unrelated to the ATP-generating activity of mitochondria or Ca2+ homeostasis. Furthermore, various conditions that increase K+ accumulation in the mitochondrial matrix (activation of ATP- or Ca2+-dependent K+ channels as well as inhibition of the K+ efflux pathway via the K+/H+ exchanger) induce a similar mechanical response. Modulators of mitochondrial function that augment isometric force also cause swelling of mitochondria in the vicinity of myofibrils in situ, as shown by confocal microscopy. Osmotic compression of intracellular structures abolishes the effect of mitochondria-induced force modulation, suggesting a mechanical basis for the interaction between the organelles. These findings suggest a novel mechanism for cellular regulation of myofibrillar function, whereby increases in mitochondrial volume can impose mechanical constraints inside the cell, leading to an increase in force developed by myofibrils.

Adenosine Triphosphate↗
PubMed1984

Molecular mechanism for the production of multiple forms of MM creatine kinase.

Incubation of human, canine or rabbit MM creatine kinase with carboxypeptidase-N or B resulted in the production of 2 additional enzyme forms with increased anodal migration on polyacrylamide gels. The C-terminal amino acid of tissue MM creatine kinase from all 3 species was shown to be lysine, a specific substrate for carboxypeptidase-N and B.

Amino Acids↗
PubMed2000

Opposite transitions of chick brain catalytically active cytosolic creatine kinase isoenzymes during development.

Postnatally the rat brain synthesizes catalytic forms of muscle type (MM) and heart type (MB) creatine kinase (CK), besides the supposedly sole type vertebrate brain-specific (BB) CK. We intended to demonstrate that in Rhode Island chicken brain, cytosolic (c) CK isoenzymatic transitions. (for example BB-CK is followed by the appearance of MB-CK and MM-CK during muscle differentiation), can also occur during development and aging. Cytosolic post 125000 x g, mitochondrial CK-free, brain samples were obtained for zone electrophoresis separation and identification of catalytically active cCK isoforms. BB-CK was never found during chicken brain ontogeny. Against the accepted view, an opposite isoenzyme transition pattern from MM through BB-CK was found in the chicken embryonic brain from the very early stages of development up to day 2 post-hatching. At very early stages of chicken brain ontogeny constitutive MM- and MB-CK isoenzymes were present before the advent of creatine. It seems to be that typical and atypical brain MM- and MB-CK could be working as ATPases in the absence of creatine before embryonic stage 28 (day 5.5) and/or such CK isoforms may begin to form part of the slow component b in developing early neurons and later in the nuclei of glial cells to be used by the CK/phosphocreatine (PC) system as the neural tissues mature. The post-hatching transition pattern showed simultaneous expression of more than one CK isoenzyme within the same neural sample as in post-natal rat brain, presumably due to regional differential transphosphorylation requirements. Strain-dependent enzymatic specific activities have been reported in several species. Since equivalent values of brain CK specific activity were obtained previously from the embryonic plateau phase of CK activity during White Leghorn development, and those from Rhode Island brain neurons cultured 11 days, we compared if, in vivo, a similar brain CK specific activity pattern was physiologically equivalent during Rhode Island and White Leghorn chicken ontogeny. We found quantitatively different strain-specific CK specific activity patterns during this period. Rhode Island brain CK activity values were approximately 4.5-fold those of White Leghorn ones. This indicates that production of energy from anaerobic metabolism and transphosphorylation by the CK/PC system to synthesize ATP more efficiently is strain-specific. In Rhode Islands, there was an age-dependent increase of CK specific activity, mostly in older animals (440% above the value found during the embryonic plateau), when the Krebs cycle and glycolysis lose capacity. During adult life and aging, under physiological conditions, the three CK isoenzymes may participate in diverse functions of the different cell compartments of brain glia and neurons with regard to their high and fluctuating energy demands that are not completely covered by anaerobic and aerobic glycolisis.

Animals↗
PubMed2001

Changes in the mitochondrial proteome from mouse hearts deficient in creatine kinase.

Creatine kinase (CK) is an abundant enzyme, important for maintenance of high-energy phosphate homeostasis in many tissues including heart. Double-knockout CK (DbKO-CK) mice missing both the muscle (MM) and sarcomeric mitochondrial (ScMit) isoforms of CK have recently been studied. Despite a large change in skeletal muscle function in DbKO-CK mice, there is little functional change in the heart. To investigate whether there are specific changes in cardiac mitochondrial proteins associated with the loss of MM- and ScMit-CK isoforms, we have used difference gel electrophoresis (DIGE) to compare mitochondrial proteins from wild-type and DbKO-CK mice. Mass spectrometry fingerprinting was used to identify 40 spots as known mitochondrial proteins. We have discovered that the loss of MM- and ScMit-CK isoforms did not cause large scale changes in heart mitochondrial proteins. The loss of ScMit-CK was readily detected in the DbKO-CK samples. We have also detected a large decrease in the precursor form of aconitase. Furthermore, two mitochondrial protein differences have been found in the parent mouse strains of the DbKO-CK mice.

Aconitate Hydratase↗
PubMed2003

Studies on the stability of creatine kinase isozymes.

Research on the stabilizing properties of creatine kinase isozymes CK-BB, CK-MB, and CK-MM showed that minor alteration of their sequence and structure influenced their stability significantly. An analysis of the stability of the isozymes in storage after freeze drying indicates that creatine kinase isozymes are all in monomer form because of the loss of subunit interactions. Freeze-drying leads to the oxidization of CK-BB and rearrangement of CK-MB. There are also differences in the unfolding of the isozymes in urea. CK-BB and CK-MB are unfolded in lower urea concentrations than CK-MM. Differences in the thermal unfolding were also examined by differential scanning calorimetry. This paper discusses the potential biological significance of these results.

Animals↗
PubMed2002

Myositis in children with meningococcal disease: a role for tumour necrosis factor-alpha and interleukin-8?

OBJECTIVES: Myalgia is under-recognized in meningococcal disease (MCD). In septic shock, myositis is thought to be mediated by pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and interleukin-6 (IL-6) but this has never previously been studied in MCD. We aimed to demonstrate whether muscle damage mediated via TNF-alpha and other pro-inflammatory cytokines occurs in MCD, as estimated by creatine kinase skeletal muscle isoenzyme (CK-MM) and cardiac isoenzyme (CK-MB) concentrations. METHODS: A total of 68 children, median age 2.7 years, with a diagnosis of MCD were prospectively studied. Severity of disease was measured using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Severe disease was defined as a GMSPS of > or =8. TNF-alpha, IL-8, IL-6 and IL-1Ra concentrations were determined on samples taken on admission. RESULTS: CK-MM correlated significantly with TNF-alpha, IL-8 and GMSPS. There was no significant correlation between CK-MB and TNF-alpha or IL-6, but CK-MB correlated with GMSPS and IL-8. Fifty-six percent of children with MCD had evidence of muscle damage as manifested by elevated CK-MM. CONCLUSIONS: TNF-alpha and IL-8 may be potential mediators in the pathophysiology of skeletal muscle damage in MCD.

Adolescent↗
PubMed1999

Electrophoresis of creatine kinase isoforms: a highly sensitive fluorescence scanning method.

OBJECTIVE: To develop an agarose electrophoretic method for creatine kinase (CK) isoforms, using highly sensitive fluorescence scanning. METHODS: A discontinuous buffer system was used. Electrophoresis on agarose gel was performed under constant current and low voltage. CK isoforms were separated within 30 minutes and detected by fluorescence scanning. RESULTS: There were no significant differences when the activities of CK-MM were between 853.0 U/L and 14.0 U/L and those of CK-MB between 152.0 U/L and 2.4 U/L. The detection limits of stain method for CK-MM and CK-MB isoforms were 36.0 U/L and 12.3 U/L, respectively; while those of fluorescence method were 12.0 U/L and 2.1 U/L. The experimental results showed good precision for CK-MM isoforms, as well for CK-MB isoforms and isoenzymes. CONCLUSION: An agarose electrophoretic method has been developed to measure CK isoenzymes and isoforms clinically. This method is rapid, simple, sensitive, highly reproducible and inexpensive. It is suitable for general laboratories.

Creatine Kinase↗
PubMed2005

Creatine kinase isoenzyme patterns upon chronic exposure to cigarette smoke: protective effect of Bacoside A.

Cigarette smoking is implicated as a major risk factor in the development of cardiovascular and cerebrovascular diseases. Creatine kinase (CK) and its isoforms (CK-MM, MB, BB) have been advocated as sensitive markers in the assessment of cardiac and cerebral damage. Therefore, in the present study, we report the isoenzyme patterns of CK in rats upon exposure to cigarette smoke and the protective effect of Bacoside A against chronic smoking induced toxicity. Adult male albino rats were exposed to cigarette smoke and simultaneously administered with Bacoside A, the active constituent from the plant Bacopa monniera, for a period of 12 weeks. The activity of CK was assayed in serum, heart and brain, and its isoenzymes in serum were separated electrophoretically. Rats exposed to cigarette smoke showed significant increase in serum CK activity with concomitant decrease in heart and brain. Also cigarette smoke exposure resulted in a marked increase in all the three isoforms in serum. Administration of Bacoside A prevented these alterations induced by cigarette smoking. Cigarette smoking is known to cause free radical mediated lipid peroxidation leading to increased membrane permeability and cellular damage in the heart and brain resulting in the release of CK into the circulation. The protective effect of Bacoside A on the structural and functional integrity of the membrane prevented the leakage of CK from the respective tissues, which could be attributed to its free radical scavenging and anti-lipid peroxidative effect.

Animals↗
PubMed2002

Sexual dimorphism in rat cerebrum and cerebellum: different patterns of catalytically active creatine kinase isoenzymes during postnatal development and aging.

During postnatal development, maturation and aging the Wistar rat cerebrum and cerebellum synthesize, in a different sex-dependent manner, catalytically active dimeric cytosolic (c) muscle-type (MM) and heart-type (MB) creatine kinase (CK), besides the supposedly sole type brain-specific (BB) CK. In both sexes, typical and atypical neuromuscular cCK isoenzymes were present during the study for 26 months. As in rat heart, females showed more cerebral cCK variants (41%) in comparison to males. Female rats exhibited about 93% more cerebellar variants of cCK isoenzymes as compared to males. The male cerebellum showed predominantly BB- and MB-CK during the whole study in comparison to the female one that contained all neuromuscular cCK variants. Only female rats showed decreases and increases of cerebral CK specific activity. In contrast to males, coinciding with the weaning period, cerebral female CK activity decreased 45% from 14 to 21 days and increased about 3-fold in female rats and only 1.3-fold in males from 21 to 45 days of age. Contrary to the remarkable 4-fold increase of chicken brain CK specific activity exhibited at old age, the rat did not show another cerebral CK activity increase during senescence in either sex. However, sex differences of CK specific activity appeared in the cerebellum at all ages. From the sex-specific plateau phase at 45-60 days until 2.2 years of age, about a 41% independent increase of cerebellar CK specific activity was observed in both sexes. After puberty, the differential cerebellum-cerebrum values of CK specific activity were higher for female rats than males during youth, adulthood and senescence. The present work shows that in rat cerebrum and cerebellum, production of ATP through anaerobic transphosphorylation by the CK/PC system is sex-and age-specific, especially in the cerebellum, when glycolysis and the Krebs cycle lose capacity. As in rat heart, under physiological conditions at all ages the several cCK isoenzymes do participate in a gender-specific manner, in favor of females, in diverse functions of the different cell compartments of glial and neuronal cells with regard to their high and fluctuating energy demands not completely covered by anaerobic and aerobic glycolysis.

Aging↗
PubMed2004

Expression of muscle creatine kinase gene of mice and interaction of nuclear proteins with MEF-2, E boxes and A/T-rich elements during aging.

The changes in the expression of muscle creatine kinase (MCK) gene in the heart and skeletal muscle of mice during aging were studied. Its expression declines as a function of age in the heart, however, no age-related change is observed in the skeletal muscle. The cis-acting elements, MEF-2, E boxes and A/T rich elements present in the enhancer region of the mouse MCK gene are known to regulate the expression of the gene. Hence, these elements were subcloned and electrophoretic mobility shift assay was carried out to investigate the changes in the binding of the nuclear trans-acting protein factors of the heart with these elements as a function of age. These factors showed specificity for the respective cis-acting elements. Furthermore, the binding of these factors was found to decrease during aging which may contribute to the age-related decline in the expression of the MCK gene and activity of the heart.

AT Rich Sequence↗
PubMed2005

In vitro measurement of enzymatic markers as a tool to detect mouse cardiomyocytes injury.

Primary cultures of cardiomyocytes represent a useful model for analyzing cardiac cell biology as well as pathogenesis of several cardiovascular disorders. Our aim was to standardize protocols for determining the damage of cardiac cells cultured in vitro by measuring the creatine kinase and its cardiac isotype and lactate dehydrogenase activities in the supernatants of mice cardiomyocytes submitted to different protocols of cell lysis. Our data showed that due to its higher specificity, the cardiac isotype creatine kinase was the most sensitive as compared to the others studied enzymatic markers, and can be used to monitor and evaluate cardiac damage in in vitro assays.

Animals↗
PubMed1986

The isoelectric focusing of creatine kinase variants: II. The heterogeneity of creatine kinase in human serum with normal and elevated catalytic concentrations.

An effective and reliable method for the quantitative estimation of creatine kinase-MB, creatine kinase-MM variants and mitochondrial forms of creatine kinase in serum is presented. The high resolving power of isoelectric focusing allows the use of tetrazolium salts and meldola blue for the quantitative measurement without interfering non-specific reduction. The addition of thiol compounds to the agarose medium increases the sensitivity of the method, due to the inhibition of sulfhydryl group oxidation, and prevents enzyme degradation, which is a possible cause of an artificial heterogeneity. Depending upon the type of muscle and the degree of cell damage, we found 3-4 creatine kinase-MM sub-bands in sera with activities below 80 U/l. At elevated creatine kinase activities 3-11 creatine kinase-MM sub-bands were found. The appearance of creatine kinase-MB in serum indicates that damage has occurred to certain organs, especially the cardiac muscle. An organ with moderate or massive cell damage could release, in addition to the sarcoplasmatic creatine kinase variants, other forms with more alkaline isoelectric points (mitochondrial creatine kinase). The presence of such bands in serum of patients correlates with poor prognosis. Besides the separation of creatine kinase-MM sub-bands, creatine kinase-MB, creatine kinase-BB and of macroforms 1 and 2, the advantage of this method is the detection of mitochondrial creatine kinase forms, which in cellulose acetate electrophoresis migrate with creatine kinase-MM.

Catalysis↗
PubMed1997

Denaturation by guanidinium chloride of dimeric MM-creatine kinase and its proteinase K-nicked form: evidence for a multiple-step process.

Cytosolic MM-creatine kinase is a homodimeric protein. Each monomer can be cleaved by proteinase K at an exposed surface loop, into two fragments K1 and K2, which remain associated. The nicked protein is thus a heterotetrameric protein, named (K1K2)2, made up of two heterodimers K1K2 linked together by their K1 subunit. In non-denaturing conditions, the cleaved protein does not present any measurable difference compared with uncleaved MM-creatine kinase, except for the loss of enzymatic activity. Comparative equilibrium denaturation of the two oligomeric proteins by guanidinium chloride indicates a multistep process with formation of either compact monomer or compact K1K2 dimer, a molten globule and a pre-molten globule state. In the case of the nicked-enzyme, the molten globule is composed of the two peptides K1 and K2, whereas in the pre-molten globule the interactions between K1 and K2 are too weak to maintain their cohesion. At low guanidinium chloride concentration, the proteinase K-nicked protein exhibits a higher accessibility of one of its tryptophan accompanied by a small decrease in its molar ellipticity suggesting a secondary structure loosening of the K1 peptide. Our results suggest that K1 and K2 are not strictly autonomous unfolding units and thus cannot be considered as independent domains.

Animals↗
PubMed1987

Creatine kinase isoform analysis in the detection and assessment of thrombolysis in man.

Recent demonstrations of the efficacy of intravenous thrombolytic therapy in acute myocardial infarction have emphasized the need for a noninvasive index of successful reperfusion. The tissue form of MM creatine kinase (MM3) is known to undergo posttranslational conversion to modified forms MM2 and MM1 after release into the plasma following acute infarction. Since this conversion is rapid, sustained elevation of plasma MM3 may be a marker of the prolonged creatine kinase release characteristic of nonreperfused infarction. Therefore, we investigated the rate of decline of plasma MM3 in a consecutive series of patients undergoing thrombolytic therapy of acute myocardial infarction, all of whom underwent acute angiography to assess treatment success, as well as in 30 conventionally treated patients. Among 55 patients with angiographically documented successful reperfusion (group IA), the rate of decline of MM3 was 4.18 +/- 1.25%/hr (mean +/- SD); in contrast, the rate of decline was 2.37 +/- 1.11%/hr in 39 patients with angiographically documented unsuccessful reperfusion (group IB) and 1.77 +/- 1.46%/hr among the 30 patients receiving conventional treatment (group II) (p less than .001 for groups IB and II vs group IA). A cutoff value of 3.1%/hr minimized the overlap between the groups; 48/55 (87%) patients with successful reperfusion had a rate of decline of MM3 of 3.1%/hr or more, while 29 of 39 (74%) patients in whom thrombolysis was unsuccessful and 27 of 30 (90%) patients receiving conventional treatment had a rate of decline less than 3.1%/hr (p less than .001 for groups IB and II vs group IA).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗