Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1979 De Bold showed that the numbers of atrial specific granules varied with changes in water and electrolyte balance of the whole animal. Two years later, he showed that atrial extracts had a natriuretic effect. The active principle has now been identified as a polypeptide formed by cleavage of a larger precursor molecule. The rate of release of atrial natriuretic peptide-like immunoreactive material by the isolated, perfused rat heart has been shown to be increased when the right atrial pressure is raised. The mechanism of release remains, however, unknown. We describe, here, experiments which show a transient release of atrial natriuretic peptide-like immunoreactive material from isolated rat atria subjected to a constant load in an organ bath. The release appears to be specific in that it is not accompanied by a parallel release of other peptides contained in nerve fibres or of creatine kinase contained in myocytes.
J Mol Cell Cardiol 1987 Mar
PMID:Release of atrial natriuretic peptide-like immunoreactive material during stretching of the rat atrium in vitro. 295 22

The nucleotide sequence of cloned DNA corresponding to full-length mouse muscle creatine kinase mRNA has been determined. This 1415 base pair DNA sequence and the deduced 381 amino acid sequence of the protein have been compared to creatine kinase sequences from other vertebrate species and to invertebrate guanidino kinase sequences. These comparisons show that the vertebrate muscle creatine kinases constitute a remarkably conserved protein family with a unit evolutionary period of 30. The creatine kinases also retain marked sequence similarity with the more distantly related invertebrate guanidino kinases. A portion of the sequence, presumably part of the ATP binding site, shows similarity to other nucleotide binding proteins with diverse functions. Comparisons of the untranslated regions of the creatine kinase cDNA sequences show that the 5' untranslated regions are more highly conserved than are the 3' untranslated regions; this may point to some regulatory function in the 5' region.
J Mol Evol 1985
PMID:The mouse muscle creatine kinase cDNA and deduced amino acid sequences: comparison to evolutionarily related enzymes. 300 72

A system to study mismatch repair in vitro in HeLa cell extracts was developed. Preformed heteroduplex plasmid DNA containing two single base pair mismatches within the SupF gene of Escherichia coli was used as a substrate in a mismatch repair assay. Repair of one or both of the mismatches to the wild-type sequence was measured by transformation of a lac(Am) E. coli strain in which the presence of an active supF gene could be scored. The E. coli strain used was constructed to carry mutations in genes associated with mismatch repair and recombination (mutH, mutU, and recA) so that the processing of the heteroduplex DNA by the bacterium was minimal. Extract reactions were carried out by the incubation of the heteroduplex plasmid DNA in the HeLa cell extracts to which ATP, creatine phosphate, creatine kinase, deoxynucleotides, and a magnesium-containing buffer were added. Under these conditions about 1% of the mismatches were repaired. In the absence of added energy sources or deoxynucleotides, the activity in the extracts was significantly reduced. The addition of either aphidicolin or dideoxynucleotides reduced the mismatch repair activity, but only aphidicolin was effective in blocking DNA polymerization in the extracts. It is concluded that mismatch repair in these extracts is an energy-requiring process that is dependent on an adequate deoxynucleotide concentration. The results also indicate that the process is associated with some type of DNA polymerization, but the different effects of aphidicolin and dideoxynucleotides suggest that the mismatch repair activity in the extracts cannot simply be accounted for by random nick-translation activity alone.
Mol Cell Biol 1987 Jan
PMID:DNA mismatch repair detected in human cell extracts. 303 61

In hypoxic-reoxygenation injury, Ca2+ overload is preceded by disturbed Na+ balance, with low activity of the Na+ pump during hypoxia and during reoxygenation. Failure to correct Na+ content rapidly upon reoxygenation might lead to Ca2+ overload by Na+-Ca2+ exchange. This possibility was tested in energy-replete myocardium by perfusing with low K+ (0.6 mM) medium to inhibit the Na+ pump throughout a two-stage procedure with low Ca2+ (0.15 mM) in the perfusate, so that Na+ loading occurred prior to excess Ca2+ uptake, as is the case in hypoxia, then with normal Ca2+ (1.3 mM) to allow Ca2+ uptake, as occurs in reoxygenation after hypoxia. Twenty minutes of Na+-loading (stage a) produced cell Na+ and tissue K+ levels similar to those after 40 min hypoxia. In stage b, hearts rapidly developed Ca2+ overload (12.6 +/- 0.90 microns/g dry wt), low ATP (4.8 +/- 0.8 microns/g dry wt), and creatine kinase release (peak 3.5 +/- 1.2 U/min/g dry wt). These values were comparable to those occurring with reoxygenation after 40 min hypoxia (Ca2+ 10.1 +/- 1.09 microns/g dry wt, ATP 6.3 +/- 0.8 microns/g dry wt, creatine kinase peak 2.1 +/- 0.5 U/min/g dry wt). Contractile failure at high resting tension occurred in both groups. In contrast, hearts recovered well from a period of Na+ pump inhibition which was only temporary. This suggests that Na+-Ca2+ exchange could account for Ca2+ overload in reoxygenation injury on the basis of Na+ pump depression developing during hypoxia and sustained in reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1987 May
PMID:Sodium imbalance as a cause of calcium overload in post-hypoxic reoxygenation injury. 304 Oct 8

The oxygen paradox refers to the abrupt release of cytoplasmic enzymes and severe cellular disruption that occurs following reoxygenation of anoxic perfused hearts. In this study, the ability of a series of oxygen-derived free radical inhibitors and scavenging agents to protect isolated perfused rat hearts from the oxygen-induced enzyme release following 30 or 60 mins of anoxic perfusion (oxygen paradox) and cumene hydroperoxide-induced injury was evaluated. Malondialdehyde (MDA) release, an indicator of lipid peroxidation, and creatine kinase (CK) release, an indicator of cellular injury, were monitored. We evaluated five agents previously reported to scavenge or inhibit the formation of oxygen free radicals. The putative hydroxyl radical scavengers dimethylthiourea (DMTU) and mannitol; catalase, an agent protective against peroxide injury; allopurinol, an inhibitor of xanthine oxidase; and albumin, a non-specific protein control, were evaluated. Coronary flow rates and myocardial temperature were continuously monitored to ensure uniform perfusion conditions. The MDA assay was carefully monitored by constructing standard curves on each experimental day. Addition of 20 microM cumene hydroperoxide to oxygenated perfused hearts caused peroxidative cell injury as evidenced by significant MDA and CK release in the coronary effluent. DMTU and catalase provided near complete protection from cumene hydroperoxide-induced cell injury but did not reduce CK release from hearts subjected to either the mild (30-min) or the severe (60-min) oxygen paradox (reoxygenation-induced injury). Allopurinol caused a significant reduction in MDA release but not CK release from oxygen paradox-injured hearts. Allopurinol and albumin had no significant effect on MDA release from cumene-hydroperoxide-injured hearts. Catalase (300 U/ml) caused a mild but not statistically significant reduction in MDA release from cumene hydroperoxide injury but did not provide protection from the oxygen paradox at either injury level. Mannitol (120 mM), in contrast to DMTU, was ineffective in reducing cumene-induced injury but showed a significant protective effect against oxygen paradox-induced damage. It is concluded that the ability of mannitol to reduce reoxygenation-induced CK release in the oxygen paradox may be due to its osmotic activity and consequent ability to prevent cellular swelling rather than its activity as an oxygen-free radical scavenger.
J Mol Cell Cardiol 1987 Jun
PMID:Effects of the free radical scavenger DMTU and mannitol on the oxygen paradox in perfused rat hearts. 311 97

The effect of thyroid hormone on cell contractility, myosin subunit composition and creatine kinase activity was explored in cultured rat myocytes. Triiodothyronine (5 nM) was administered to neonatal rat heart myocytes grown in chemically defined medium. The hormone induced a 30% enhancement in the rate of cell beating and a complete transition from beta- to alpha-myosin heavy chain synthesis. Myosin light chains as well as creatine kinase activity and isozymic distribution were unaffected by the hormone. The arrest of spontaneous contraction by either membrane depolarization or Ca2+ channel blockage did not interfere with the shift towards alpha-myosin heavy chain predominance. We conclude that thyroid regulation of myosin subunits is confined to the molecule heavy subunits and occurs irrespective of cell contraction. Furthermore, the genomic expression of creatine kinase is not regulated by thyroid hormone.
J Mol Cell Cardiol 1988 Jul
PMID:Effect of triiodothyronine on cultured neonatal rat heart cells: beating rate, myosin subunits and CK-isozymes. 317 51

Five monoclonal antibodies (CKM-B07, F12, D08, H09 and G01) against porcine creatine kinase (CK; EC 2.7.3.2) MM isoenzyme, which inhibit the enzymatic activity, were prepared. The hybridomas which produced monoclonal antibodies were screened by direct measurement of the inhibitory activity of their culture supernatant. Only two of them, however, were found to be measurable by an enzyme-linked immunosorbent assay with porcine CK-MM as an antigen. CKM-G01 inhibited 100% porcine CK-MM activity, while the others, 73-87%. On the other hand, only CKM-H09 inhibited porcine CK-BB activity (15%). CKM-F12 and D08 inhibited more than 50% CK-MB activity, whereas they did not inhibit CK-BB activity. The monoclonal antibodies were also tested for bovine, rabbit and human CK-MM. All the antibodies inhibited bovine and human CK-MM activity as well. In particular, CKM-G01 was found to exhibit more than 98% inhibition of all CK-MM activity tested, indicating that a common or very similar epitope which affects the activity is present on these enzymes. Admixing of CKM-B07 with other antibodies effected synergisms in inhibition, not only to porcine CK-MM activity but also to human CK-MM activity. A mixture of CK-B07 and G01 inhibited 100% human CK-MM activity, suggesting applicability of these monoclonal antibodies to clinical laboratory diagnosis.
Mol Cell Probes 1988 Jun
PMID:Creatine kinase-inhibiting monoclonal antibodies: preparation and characterization of porcine MM isoenzyme-specific antibodies. 317 59

Rats were fed a diet containing beta-guanidinopropionic acid (GP), an inhibitor of creatine transport. After 6 to 8 weeks of feeding the myocardial creatine (Cr) and phosphocreatine (PCr) stores were severely depleted while ATP content was normal. Hearts of GP-treated rats perfused according to Neely's working heart model revealed clear cardiac contractile failure: the maximal work capacity at a stepwise increase in resistance as well as the maximal oxygen consumption were 32 to 40% less in the GP group. The cardiac failure in GP-treated working hearts was associated with a rise in the left ventricular diastolic pressure, which could cause a diminished cardiac output probably due to impaired LV filling. The extent of the contractile failure was found to depend on functional load and on the degree of Cr (PCr) substitution. The energy fluxes through creatine kinase measured by the 31P-NMR saturation transfer technique were diminished by a factor of two after substitution of 90% of creatine, but still exceeded the rate of ATP turnover. The results are compatible with the concept of phosphocreatine pathway for intracellular energy transport and show that PCr is an important high energy phosphate compound for cardiac contractile function.
J Mol Cell Cardiol 1988 Jun
PMID:The cardiac contractile failure induced by chronic creatine and phosphocreatine deficiency. 321 3

Functional states of cardiac contractile apparatus and mitochondria were studied in hereditary cardiomyopathic hamsters (CHF 146) and control golden hamsters using cardiac fibers skinned by two different techniques. The Triton X-100 skinned fibers obtained from diseased animals of 175 to 200 days old, or from control animals, demonstrated the same resting and maximal Ca-activated tensions, the same stiffness, the same rate of tension recovery after quick stretch; the fibers from cardiomyopathic animals differed only by a slightly increased calcium sensitivity. Functional activity of myofibrillar creatine kinase in cardiomyopathy was decreased as indicated by a smaller shift in the pMgATP/rigor tension curve to lower [MgATP] in the presence of phosphocreatine and by a slower rate of the tension recovery after quick stretch in the presence of phosphocreatine and ADP (without ATP). The saponin-skinned fibers allow evaluation of the respiration properties of the total tissue mitochondria. Data obtained in the preparations isolated from diseased animals of two ages (75 to 100 and 175 to 200 days) showed that the ratio of maximal ADP-stimulated respiration rate to the respiration rate in the absence of ADP (an analog of respiration control index) was unchanged in myopathy as compared with age-matched controls. However stimulation of respiration after an addition of creatine at submaximal ADP concentration was observed to be respectively 1.45 times and 3.5 times less in the preparations from younger and older myopathic animals as compared with their respective controls, thus indicating the impairment of functional coupling between mitochondrial creatine kinase reaction and oxidative phosphorylation. These results suggest that hereditary cardiomyopathy is associated with alterations in myocardial creatine kinase system, while myofilaments and mitochondria preserve their basic functional properties.
J Mol Cell Cardiol 1988 Apr
PMID:Functional state of myofibrils, mitochondria and bound creatine kinase in skinned ventricular fibers of cardiomyopathic hamsters. 326 69

Muscle creatine kinase (MCK) is induced to high levels during skeletal muscle differentiation. We have examined the upstream regulatory elements of the mouse MCK gene which specify its activation during myogenesis in culture. Fusion genes containing up to 3,300 nucleotides (nt) of MCK 5' flanking DNA in various positions and orientations relative to the bacterial chloramphenicol acetyltransferase (CAT) structural gene were transfected into cultured cells. Transient expression of CAT was compared between proliferating and differentiated MM14 mouse myoblasts and with nonmyogenic mouse L cells. The major effector of high-level expression was found to have the properties of a transcriptional enhancer. This element, located between 1,050 and 1,256 nt upstream of the transcription start site, was also found to have a major influence on the tissue and differentiation specificity of MCK expression; it activated either the MCK promoter or heterologous promoters only in differentiated muscle cells. Comparisons of viral and cellular enhancer sequences with the MCK enhancer revealed some similarities to essential regions of the simian virus 40 enhancer as well as to a region of the immunoglobulin heavy-chain enhancer, which has been implicated in tissue-specific protein binding. Even in the absence of the enhancer, low-level expression from a 776-nt MCK promoter retained differentiation specificity. In addition to positive regulatory elements, our data provide some evidence for negative regulatory elements with activity in myoblasts. These may contribute to the cell type and differentiation specificity of MCK expression.
Mol Cell Biol 1988 Jan
PMID:The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer. 333 66


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