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)

Three structurally distinct amphiphiles palmitic acid, oleic acid, and palmityl carnitine were studied to determine their effects on sodium dependent calcium uptake by purified cardiac sarcolemmal vesicles (PSL). Sodium dependent calcium uptake by PSL when studied over a 20 min reaction period was composed of an initial rapid uptake (20.9 +/- 0.93 nmol/mg X 30 s, mean +/- S.E. n = 20) a plateau in calcium content (42.4 +/- 3.2 nmol/mg, mean +/- S.E. n = 20) and a slow spontaneous release characterized by a first order rate constant of 0.68 +/- 0.08/h (mean +/- S.E. n = 18). Both palmityl carnitine and palmitic acid inhibited, whereas oleic acid stimulated initial calcium uptake. All three amphiphiles shortened the time to peak calcium content, inhibited peak calcium content and increased the rate constant for calcium release. All these effects were observed at fatty acid: membrane phospholipid mole ratios of 0.67 : 1 to 1.67 : 1 for oleic acid and palmityl carnitine and 0.02 : 1 to 0.42 : 1 for palmitic acid. These effects do not reflect disruption of membrane vesicle structure and may be explained, at least in part, by amphiphile induced increases in sarcolemmal membrane ion permeability. Although amphiphile accumulation has been implicated in the pathogenesis of cellular abnormalities in the ischemic myocardium, this study has shown that large amounts of amphiphile relative to membrane lipid are required to alter sarcolemmal membrane function in vitro.
J Mol Cell Cardiol 1985 Sep
PMID:Effects of fatty acids on Na/Ca exchange in cardiac sarcolemmal membranes. 404 47

The cell cycle kinetics of uninfected and feline leukemia virus-infected canine lymphoma cell lines were determined by autoradiography (PLM method) as follows: DT-5: generation time (TC), 15.2 h; pre-synthetic gap phase (TG1), 3.2 h; DNA-synthetic phase (TS), 8.2 h; post-synthetic gap ph se (TG2), 3.3 h; visible mitotic phase (TM), 0.5 h. 11028: TC, 13.6 h; TG1, 1.9 h; TS, 7.7 h; TG2, 3.4 h; TM, 0.6 h. 11028+FeLV (11028 productively infected with feline leukemia virus): TC, 11.2 h; TG1, 0.2 h; TS, 8.3 h; TG2, 2.1 h; TM, 0.6 h. Exposure of the lymphoma cell lines to methotrexate (MTX) in vitro produces dose-related increases in cellular volume, associated with reductions in cellular proliferation. The relative sensitivities of these cell lines to MTX, measured by the ID50 MTX concentrations for DT-5, 11028, and 11028+FeLV are 118 nM, 122 nM, and 28 nM respectively. The cell kinetic effects of the ID50 MTX concentrations added to cultures of lymphoma cells pulse-labeled with tritiated thymidine are an approximately 2-h prolongation of TC, attributable to a lengthening of TS, with other cell cycle phases not significantly altered. These cell lines are highly tumorigenic when transplanted into the cheek pouches of immunosuppressed hamsters, with inocula of 10(4) cells producing rapidly growing, well vascularized tumors.
Virchows Arch B Cell Pathol Incl Mol Pathol 1980
PMID:Cell cycle kinetics of uninfected and feline leukemia virus-infected canine lymphoma cell lines: effects of methotrexate treatment. 610 97

A spot test has been developed for detecting substances that enhance the transposition of Tn9 in Escherichia coli. Phage lambda::Tn9-infected cells were plated on chloramphenicol media and a drop of the test substance was placed at the center of the plate. Following incubation, chloramphenicol-resistant colonies appeared due to the transposition of Tn9 to the bacterial chromosome. By comparing the test plate and a control plate with respect to the number and distribution of colonies, the effect of the test compound can be evaluated. Out of over 100 compounds tested, acetate, two detergents (Brij 58 and Nonidet P40) and dimethylsulfoxide were found to enhance transposition 3-20 fold. Acetate was also found to enhance the transposition of Tn5 and Tn10. The stimulating effect of Brij 58 was lost when palmitic acid was added with the Brij 58. The nature of these substances, which we refer to as "transposagens", suggests an involvement of lipid or membrane in the transposition process.
Mol Gen Genet 1983
PMID:Detection of chemicals that stimulate Tn9 transposition in Escherichia coli K12. 630 65

We have previously reported the isolation and characterization of Chinese hamster ovary (CHO) cell mutants defective in the internalization of ricin (Ray, B., and Wu, H.C. (1982) Mol. Cell. Biol. 2, 535-544). These mutants also do not exhibit the enhancement of ricin internalization by nigericin pretreatment at a low concentration, which is observed in the wild-type CHO cells. An analysis of somatic cell hybrids between the mutant and the toxin-sensitive wild-type CHO cell line shows that all of the phenotypes associated with the toxin resistance mutation are dominant in the hybrid cell lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [3H]palmitic acid-labeled cell extracts from the mutant and toxin-resistant hybrid cell lines has revealed an increased incorporation of [3H] palmitic acid into two proteins with apparent molecular weights near 30,000 in the mutant and hybrid cells as compared to that in the wild-type cell line. Our studies indicate that these two fatty acyl proteins might be related to a dominant mutation(s) which results in a decreased uptake of ricin.
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PMID:Genetic and biochemical analysis of mutation(s) affecting ricin internalization in Chinese hamster ovary cells. 649 Jun 39

We have previously detected in TMV-infected cells virus-specific informosome-like ribonucleoproteins (vRNP) that differed in the CsCl buoyant density from mature TMV particles. It is shown in the present work that [3H]uridine-labelled TMV-specific structures, when fractionated in Cs2SO4, produce three types of structures, i. e. with a buoyant density of 1.23 g/cm3 (the so-called 1.23 material), 1.29 g/gm3 (mature virus) and 1.34--1.49 g/cm3 (vRNP). The 1.23 material has been investigated. The incorporation of [3H]palmitic acid and the sensitivity of this material to 0.1% Na dodecyl sulphate was interpreted to mean the presence of membrane components. Treatment of the 1.23 material Na dodecyl sulphate induces the release of the mature virus, vRNP and free viral RNA. vRNP was shown to contain genome TMV RNA (mol. weight, 2.0 x 10(6)) and a considerable amount of subgenomic TMV RNA (mol. weight, 1.1--1.3 x 10(6) and 0.6--0.8 x 10(6)). It is demonstrated that RNA isolated from vRNP codes for TMV-specific proteins and is able to hybridize with recombinant plasmid containing DNA-copy of 3'-end RNA TMV fragment (about one half of genome).
Mol Biol (Mosk)
PMID:[Virus-specific informosomes in tobacco cells infected with tobacco mosaic virus]. 670 56

Effects of free fatty acids (palmitate and linoleate) on myocardial contractility and slow action potentials (APs) were examined in Langendorff-perfused chick hearts. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated in elevated K+ (25 mM), and the concentration of Ca2+ ion was increased to 5.4 mM in order to induce slow APs. Palmitate (0.18, 0.54 or 0.72 mM) along with albumin (0.12 mM) was added to the perfusate. Albumin by itself did not affect contractility or the slow APs during normoxia and hypoxia. Under well oxygenated conditions, palmitate had no effect on contractility or the slow APs. However, palmitate accelerated the decline of contractility during hypoxia in a dose-dependent fashion. Hypoxia suppressed the slow APs, and palmitate and linoleate further exacerbated the suppression of slow APs produced by hypoxia. Nevertheless, palmitate and linoleate did not enhance the hypoxic reduction of the tissue high energy phosphate level. The present results suggest that free fatty acids elicit cardio-depressant effects on hearts through their direct action on the myocardial cell membrane (slow channels) rather than through any metabolic effects.
J Mol Cell Cardiol 1984 Mar
PMID:Enhanced suppression of myocardial slow action potentials during hypoxia by free fatty acids. 671 92

Affinity partitioning in dextran-polyethylene glycol-water biphasic systems has demonstrated that myosin has hydrophobic surface properties. In 0.5 M KCl at pH 7.5 myosin is transferred at increasing amounts to the polyethylene glycol-rich upper phase when an increasing proportion of that polymer in the system is replaced by its ester with lauric, myristic or palmitic acid. This shows that on its surface myosin has binding sites with affinity for long chain fatty acyl groups. Partition studies on the ionic strength range of 0.2-0.6 M KCl at pH 7.5 at 4 degrees C and 20 degrees C, respectively, in systems containing polyethylene glycol-palmitate showed that the affinity of myosin for the palmitate group becomes greater with (1) an increase in ionic strength, and (2) an increase in temperature at constant ionic strength. The affinity of myosin for the palmitate group also increases with a decrease in the pH in the range of 5.6-8.5. The increase in the affinity of myosin for the palmitate group parallels the increase in the tendency of myosin to self-interact and yield filaments.
Mol Cell Biochem 1982 Oct 18
PMID:Hydrophobic surface properties of myosin in solution as studied by partition in aqueous two-phase systems: effects of ionic strength, pH and temperature. 714 45

Kimura mistook ambiguous maximum parsimony codons for wrong codons. The maximum parsimony method performed well as judged by the two classes of serine codons (which can not be connected by silent mutations) on comparing the parsimony codons for serines in human, rabbit, and mouse alpha hemoglobin chains to actual codons determined by nucleotide sequencing. In genealogical reconstructions involving 247 eucaryotic globins, the maximum parsimony distances separating the contemporary sequences show that Kimura's Poisson and Dayhoff's PAM estimates of rate of globin evolution miss most of the superimposed replacements and are therefore seriously in error. Nor is Kimura's constant rate assumption and his belief in a single origin of myoglobin supported. Lamprey myoglobin appears to be most like lamprey hemoglobin, while gnathostome myoglobin seems closest to gnathostome hemoglobin. It was found that the three types of gnathostome globins (Mb, alpha Hb, beta Hb) evolved between the shark-boney vertebrate and bird-mammal ancestors at a much faster rate than from the latter ancestor to the present. The data indicate that rates were exceedingly fast during the origin of these globin chains because a high proportion of substitutions were adaptive. It was concluded that wherever strong stabilizing selection acts on a protein, somewhere in the past positive Darwinian selection must have spread the amino acid substitutions now being preserved.
J Mol Evol 1981
PMID:Globin evolution was apparently very rapid in early vertebrates: a reasonable case against the rate-constancy hypothesis. 725 36

To explore the molecular basis of the biochemical differences among acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and their alternative splicing and allelic variants, we investigated the acylation phase of cholinesterase catalysis, using phosphorylation as an analogous reaction. Rate constants for organophosphate (DFP) inactivation, as well as for oxime (PAM)-promoted reactivation, were calculated for antibody-immobilized human cholinesterases produced in Xenopus oocytes from natural and site-directed variants of the corresponding DNA constructs. BuChE displayed inactivation and reactivation rates 200- and 25-fold higher than either product of 3'-variable AChE DNAs, consistent with a putative in vivo function for BuChE as a detoxifier that protects AChE from inactivation. Chimeric substitution of active site gorge-lining residues in BuChE with the more anionic and aromatic residues of AChE, reduced inactivation 60-fold but reactivation only 4-fold, and the rate-limiting step of its catalysis appeared to be deacylation. In contrast, a positive charge at the acyl-binding site of BuChE decreased inactivation 8-fold and reactivation 30-fold. Finally, substitution of Asp70 by glycine, as in the natural 'atypical' BuChE variant, did not change the inactivation rate yet reduced reactivation 4-fold. Thus, a combination of electrostatic active site charges with aromatic residue differences at the gorge lining can explain the biochemical distinction between AChE and BuChE. Also, gorge-lining residues, including Asp70, appear to affect the deacylation step of catalysis by BuChE. Individuals carrying the 'atypical' BuChE allele may hence be unresponsive to oxime reactivation therapy following organophosphate poisoning.
Brain Res Mol Brain Res 1995 Jul
PMID:Successive organophosphate inhibition and oxime reactivation reveals distinct responses of recombinant human cholinesterase variants. 747 18

To identify elements participating in the process of transformation, a bank of genetically altered mutants of Streptococcus pneumoniae with defects in exported proteins was assessed for a decrease in transformation efficiency. One mutant consistently transformed 10-fold less than the parent strain. Sequence analysis and reconstitution of the altered locus revealed a gene, plpA (permease-like protein), which encodes a putative substrate-binding protein belonging to the family of bacterial permeases responsible for peptide transport. The derived amino acid sequence for this gene was 80% similar to AmiA, a peptide-binding protein homologue from pneumococcus, and 50% similar over 230 amino acids to Spo0KA which is a regulatory element in the process of transformation and sporulation in Bacillus subtilis. PlpA fusions to alkaline phosphatase (PhoA) were shown to be membrane associated and labelled with [3H]-palmitic acid, which probably serves as a membrane anchor. Experiments designed to define the roles of the plpA and ami determinants in the process of transformation showed that: (i) mutants with defects in plpA were > 90% transformation deficient while ami mutants exhibited up to a fourfold increase in transformation efficiency; (ii) compared to the parental strain, the onset of competence in an ami mutant occurred earlier in logarithmic growth, whereas the onset was delayed in a plpA mutant; and (iii) the plpA mutation decreases the expression of a competence-regulated locus. Since the permease mutants would fail to bind specific ligands, it seems likely that the substrate-permease interaction modulates the process of transformation.
Mol Microbiol 1994 Jun
PMID:Peptide permeases modulate transformation in Streptococcus pneumoniae. 752 29


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