Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P67775 (alpha isoform)
 797 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S-100a0 protein, the alpha alpha isoform of the S-100 family, stimulates basal (Mg2+-activated) adenylate cyclase (AC) activity associated with the sarcolemma, longitudinal tubules and terminal cisternae of rat skeletal muscle cells. The stimulatory effect of S-100a0 on AC activity is maximal around 5 microM S-100a0 and half-maximal around 0.2 microM S-100a0. Also, the stimulatory effect is greatest on the AC activity associated with the terminal cisternae than on the other membrane fractions studied. These data are discussed in relation to the subcellular localization of S-100a0 in muscle cells.
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PMID:S-100a0 protein stimulates the basal (Mg2+-activated) adenylate cyclase activity associated with skeletal muscle membranes. 272 82

A simple procedure is described for the purification of the alpha alpha isoform of S-100 proteins (S-100a0) from porcine heart. Purification steps include the following: i) extraction of the tissue with a hypotonic medium containing EDTA; ii) ammonium sulfate fractionation (0-50%) of the extract; iii) Ca2+-dependent affinity chromatography of the supernatant obtained through the preceding step on phenyl-sepharose and elution of absorbed proteins through a two-chamber gradient of 1.0-0.0 mM CaCl2 and 0.0--1.0 mM EGTA, respectively; and iv) chromatography of the resultant S-100-containing fractions on Sephadex G-200. The yield is 20 mg S-100a0/kg porcine heart. The whole procedure takes five days and is highly reproducible. Data obtained from the phenyl-sepharose step suggest that the affinity of Ca2+ for S-100a0 increases by several orders of magnitude once the protein had interacted with that matrix. This observation is discussed in relation to the role of S-100 proteins in amplification of the Ca2+ signal. Immunocytochemical and immunoblotting analyses indicate that S-100a0 is exclusively found at the level of the sarcolemmal membranes, the membranes of the sarcoplasmic reticulum, the external mitochondrial membranes, and in the adjacent sarcoplasm. No evidence of S-100a0 being associated with the nuclei or with myofibrils has been obtained. Finally, the cardiac tissue does not contain the Triton X-100-extractable fraction of S-100 normally detected in the brain and in adipocytes. Our data suggest that S-100a0 behaves as a peripheral membrane protein in cardiac tissue.
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PMID:Cardiac S-100a0 protein: purification by a simple procedure and related immunocytochemical and immunochemical studies. 274 4

From the results of this study the following significant conclusions can be drawn. First, there are two separate inotropic responses to ouabain in the rat ventricle and the isolated rat heart resulting in a biphasic dose-response curve. Second, both the "low dose" and "high dose" inotropic responses of ouabain in the rat heart result from the inhibition of NKA, i.e., NKA is the binding site of ouabain for both "low" and "high" dose effects. Third, biphasic inotropic effects (rat ventricle) go together with alpha + and alpha (high and low affinity) isoforms of NKA, monophasic (rat atrium) with the alpha isoform (low affinity). Fourth, high extracellular calcium concentrations inhibit NKA and mask the full expression of the "low-dos" effect.
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PMID:The calcium dependence of the biphasic inotropic response to ouabain in the isolated rat heart. 283 73

Sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) is hypothesized to be involved in systemic vascular hypertension through its effects on smooth muscle reactivity and myocardial contractility. By means of RNA blot analyses of cardiac, aortic, and skeletal muscle RNAs in two rat hypertensive models, Na+,K+-ATPase alpha-subunit messenger RNA isoforms (alpha 2 and alpha 3) were shown to be deinduced in response to increased intravascular pressure. The changes were observed after 48 hours or more of experimental hypertension. Under these conditions, there is coordinate induction of another alpha isoform (alpha 1) and of beta-subunit messenger RNAs, probably in response to alterations in sodium flux rather than to elevated blood pressure.
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PMID:Isoform-specific modulation of Na+, K+-ATPase alpha-subunit gene expression in hypertension. 283 7

The developmental expression of the multiple isozymes of Na,K-ATPase in rat brain, heart, lung, kidney, and skeletal muscle from fetal (14 days gestation) to adult (55 days) was investigated at the molecular level with cDNA probes specific for the multiple catalytic alpha isoform (alpha 1, alpha 2, alpha 3) and beta subunit mRNAs. Northern and RNA slot blot analyses revealed that these mRNAs are regulated in a tissue-specific manner. The multiple alpha isoform and beta subunit mRNAs appear to be regulated coordinately during ontogenesis with maximum expression occurring between 15 and 25 days of age for brain, heart, kidney, and skeletal muscle, whereas peak expression in lung was observed between 2 and 4 days of neonatal life. Brain tissue showed between 10- and 17-fold increases in the levels of expression for the three individual alpha isoform mRNAs. The alpha 3 mRNA was found to be the predominant alpha isoform transcript in fetal as well as adult brain. Examination of heart tissue showed alpha 1 mRNA to be the major catalytic subunit during development. However, a developmentally regulated transition in alpha 2 and alpha 3 mRNA expression was observed in heart between 7 and 14 days after birth. The alpha 3 mRNA was expressed primarily in fetal and neonatal heart tissue, while alpha 2 mRNA was expressed in juvenile and adult tissue. In kidney and lung, alpha 1 mRNA was the predominant alpha isoform transcript showing temporary increases in expression of 2- and 4-fold, respectively, during development. In contrast to the other tissues, muscle expressed predominantly alpha 2 mRNA following birth, the levels increasing approximately 89-fold during myogenesis. Thus, each tissue examined exhibits a distinct pattern of expression for the Na,K-ATPase catalytic alpha isoforms during ontogenesis.
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PMID:Tissue-specific and developmental regulation of rat Na,K-ATPase catalytic alpha isoform and beta subunit mRNAs. 283 91

Expression of Na,K-ATPase catalytic alpha isoform (alpha 1, alpha 2, and alpha 3) and beta subunit genes in rodent muscle was investigated using the murine C2C12 myogenic cell line. RNA blot analyses of myoblasts revealed expression primarily of the alpha 1 mRNA and low levels of alpha 2 mRNA. Fusion of the proliferating myoblasts to form myotubes was accompanied by an approximate 12-fold induction of the alpha 2 mRNA. In contrast, expression of alpha 1 mRNA remained constant throughout myogenesis. The alpha 3 mRNA was not detected in either myoblasts or myotubes. The beta mRNA abundance also increased 2-3-fold during myotube formation. In rodent tissues, low and high affinity cardiac glycoside (e.g. ouabain) receptors have been shown to be associated with the Na,K-ATPase catalytic alpha 1 and alpha 2 isoform subunits, respectively. The existence of these two functional classes of Na,K-ATPase in myoblasts and myotubes correlated with the biphasic ouabain inhibition of Na,K-ATPase activity. Confluent myoblasts expressed primarily the alpha 1 isozyme (IC50 = 3.6 X 10(-5) M; 95% of total activity) and lesser amounts of the alpha 2 isozyme (IC50 = 1.1 X 10(-7) M; 5% of total activity). In contrast, the myotubes showed significant levels of the alpha 1 isozyme (IC50 = 4.0 X 10(-5) M; 68% of total activity) and, in addition, showed a 6-fold increase in the relative levels of the alpha 2 isozyme (IC50 = 1.1 X 10(-7) M; 32% of total activity). To quantitate further the expression of the high affinity, ouabain-sensitive alpha 2 isozyme, a whole cell [3H]ouabain-binding assay was used. Results revealed that myotubes have an approximately 6-fold greater concentration of [3H]ouabain-binding sites than myoblasts with an apparent dissociation constant (Kd) of 1.4 X 10(-7) M. The results indicate that muscle cells can express multiple isozymes of Na,K-ATPase and that expression of the alpha 2 isozyme is developmentally regulated during myogenesis.
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PMID:Differential expression of the Na,K-ATPase alpha 1 and alpha 2 subunit genes in a murine myogenic cell line. Induction of the alpha 2 isozyme during myocyte differentiation. 284 80

Prednisolone-3,20-bisguanylhydrazone (PBGH), a steroid derivative, has been shown to inhibit Na+,K+-ATPase isolated from guinea-pig heart or kidney in concentrations significantly lower than those required to inhibit the enzyme obtained from other sources. Because Na+,K+-ATPases obtained from guinea-pig heart or kidney are predominantly of the alpha isoform, the hypothesis that PBGH selectively inhibits the alpha isoform over alpha (+) isoform of the enzyme was tested. Sodium dodecylsulfate polyacrylamide gel electrophoresis of the enzyme preparations revealed the presence of only the higher mobility, alpha isoform in guinea-pig heart and ferret kidney, whereas those from guinea-pig brain, dog brain and ferret heart showed both high and low mobility isoforms corresponding to alpha and alpha (+) isoforms. Na+,K+-ATPase obtained from the guinea-pig heart was most sensitive to PBGH and those isolated from ferret heart or ferret kidney had the lowest sensitivity. Enzyme preparations obtained from dog brain, dog heart or guinea-pig brain had intermediate sensitivity. This spectrum of enzyme sensitivity to PBGH was markedly different from that to ouabain. In ferret heart Na+,K+-ATPase, a low concentration of PBGH preferentially inhibited [3H]ouabain binding to the high affinity ouabain binding sites (alpha(+) isoform). These results indicate that PBGH is not a specific inhibitor of the alpha isoforms of Na+,K+-ATPase. Affinity of the enzyme for PBGH is determined by the species and tissue rather than isoforms of Na+,K+-ATPase.
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PMID:Cardiac Na+,K+-ATPase isoenzymes: sensitivity to prednisolone bisguanylhydrazone. 285 75

Rat brain and kidney cDNA libraries were constructed and screened with a cDNA insert corresponding to the mRNA for the sheep kidney Na+,K+-ATPase catalytic subunit. The alpha-subunit cDNAs isolated from the kidney library were derived from a single class of messenger RNA, and the brain cDNAs were derived from three classes of messenger RNA. The most abundant brain cDNA, which spans 5.1 kilobases, encodes the alpha(+) form of the enzyme. The second most abundant brain cDNA, which spans 3.65 kilobases, is identical with that of the kidney form and therefore encodes the alpha isoform. The third class of cDNA, which spans 3.55 kilobases, was present at low abundance and encodes an isoform of the alpha-subunit, designated alpha III, which has not been identified previously. The complete nucleotide sequence and deduced amino acid sequence for each of the brain and kidney cDNAs have been determined. In addition, we have identified a lysine-rich sequence that may function as a movable, ion-selective gate during cation binding and occlusion and have also identified several amino acid sequence variations that appear to explain some of the well-known species and tissue differences in cardiac glycoside sensitivity.
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PMID:Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain. 302 70

In vertebrate skeletal muscle, the proliferating myoblasts synthesize nonmuscle isoforms of actin, and the cells begin to express muscle-specific actin isoforms during their myogenic differentiation. To study the distributions of the actin isoforms in myogenic cells and fully differentiated skeletal muscle, we prepared a peptide antibody specific for the skeletal alpha isoform of actin and used this antibody along with an antibody specifically reactive with nonmuscle gamma actin to stain cultured myotubes and adult skeletal myofibrils by double-indirect immunofluorescence. At this level of resolution, no differences in isoform localization were seen: Both muscle and nonmuscle actins were detected in the myotubes and in the striations of mature myofibrils. Myotubes were also double-stained using immunogold electron microscopy, and the isoform distributions were determined quantitatively by counting the two sizes of gold particles that corresponded to labeling with each antibody. A quantitative analysis of immunoreactivity revealed that, although both forms were present in all actin-containing structures, nonmuscle actin was relatively more prevalent along the edges (cortical microfilaments) of the myotubes, whereas the muscle isoform predominated in the interior regions (containing forming myofibrils). Thus, we have found evidence of a heterogeneous distribution of muscle and nonmuscle actin isoforms in differentiating myogenic cells, and we have demonstrated that a nonmuscle actin isoform is a component of the muscle contractile apparatus.
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PMID:Immunolocalization of muscle and nonmuscle isoforms of actin in myogenic cells and adult skeletal muscle. 329 62

Heteroploid mouse NIH 3T3 fibroblasts and several rat fibroblast strains (Rat-1, Rat-2 and REF-52) are cell lines of special interest in the field of carcinogenesis because of their extensive use as normal cells in transformation assays for putative cancer-causing genes. Exposure of these cells to carcinogenic chemicals or oncogenic DNA produces anchorage-independent cells with retracted cytoplasms that lack actin cables. All human fibroblast strains, normal and transformed, synthesize two electrophoretic forms of actin (beta- and gamma-actin). In contrast, we discovered that early-passage mouse and rat strains synthesize abundant amounts of each of the three electrophoretic forms of actin (alpha-, beta- and gamma-actin) but mouse and rat cancer cells express only beta- and gamma-actins. We now show that in NIH 3T3 and Rat-2 fibroblasts a third actin, the smooth muscle alpha isoform, is abundantly co-expressed with beta- and gamma-actin. In every instance tested following transformation to tumorigenicity, the accumulation of alpha-actin messenger RNA and alpha-actin synthesis was greatly inhibited. Shutdown of alpha-actin expression thus appears to be a reproducible transformation-sensitive marker in rodent fibroblasts.
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PMID:Smooth muscle alpha-action is a transformation-sensitive marker for mouse NIH 3T3 and Rat-2 cells. 403 81


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