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)

Surfactant can be inhibited in vivo by plasma proteins invading the alveolar space during acute lung injury. The resistance to protein inhibition of surfactant preparations with various synthetic surfactant proteins B and C (B and C) was tested in preterm rabbits. Surfactants consisted of a palmitic acid containing phospholipid mixture (PL) with full-length SP-B peptide (B1-78), one of two SP-B mutants (Bserine and BR236C), the synthetic SP-B mimic KL4 (UCLA-KL4), a natural SP-B (Bbovine), synthetic palmitoylated SP-C peptide (C1-35), a combination of B1-78 + C1-35, a combination of BR236C + C1-35, and the clinical surfactant Survanta. Preterm rabbits born at 28 days of gestation were ventilated and received 100 mg/kg of albumin intratracheally at 30 min and 100 mg/kg of surfactant at 45 min after birth. Dynamic lung compliance (tidal volume/mean airway pressure) decreased from 0.82 to 0.57 mL/kg/cm H2O after albumin instillation and to 0.43 mL/kg/cm H2O over a 60-min period after saline placebo. Treatment with B1-78 + C1-35 and BR236C + C1-35 surfactant and Survanta returned dynamic compliance to prealbumin values, B1-78, BR236C, Bbovine, and C1-35 surfactant stabilized dynamic compliance, but PL, Bserine, and UCLA-KL4 surfactant were unable to prevent a further deterioration in dynamic compliance. These data suggest that a combination of synthetic surfactant peptides B1-78 and C1-35 and the clinical surfactant Survanta confer a high degree of resistance to surfactant inhibition by human albumin in ventilated preterm rabbits.
Mol Genet Metab 1999 Jan
PMID:Sensitivity of synthetic surfactants to albumin inhibition in preterm rabbits. 997 46

Radiolabelled methionine incorporation into synchronised Plasmodium berghei gametocytes or ookinete cultures, showed that Pbs21 is not synthesised in bloodstage parasites; synthesis was detected within three hours of induction of gametogenesis; synthesis was triggered at gametogenesis, not by fertilisation. We show native Pbs21 to be a hydrophobic membrane protein that was insensitive to cleavage by phosphatidylinositol phospholipase C (PI-PLC), but sensitive to alkaline hydroxylamine, and partially sensitive to glycosylphosphatidylinositol-dependent phospholipase D (GPI-PLD) and HNO2. 3H-myristic and palmitic acid, 3H-glucosamine and mannose incorporation indicated Pbs21 was acylated and glycosylated. Linkage of the acyl group was sensitive to HNO2, which released an acyl-phosphatidylinositol more hydrophobic than that released from P3 of Trypanosoma brucei. All these properties are consistent with the presence of a malaria-specific glycosylphosphatidylinositol (GPI) anchor. In contrast recombinant Pbs21 (rPbs21), expressed in Spodoptera frugiperda cells, was sensitive to both PI-PLC and GPI-PLD, consistent with the protein being modified by a different (S. frugiperda) GPI anchor. Brefeldin A blocked secretion of rPbs21 within a cytoplasmic reticular compartment. Following deletion of the putative GPI anchor addition site (amino acids 189 213), the protein was transported to the cell surface and secreted directly into the aqueous phase of the culture medium. Deletion of amino acids 205-213 disrupted Pbs21 processing, transport through the ER and distribution onto the cell surface. Deletion of amino acids 1-28 prevented transport of Pbs21 into the ER. This suggests that correct processing of the GPI anchor in the ER-Golgi network is essential for the successful secretion of the recombinant protein, which is additionally dependent upon an N-terminal secretory signal sequence.
Mol Biochem Parasitol 1999 Jan 25
PMID:The biosynthesis and post-translational modification of Pbs21 an ookinete-surface protein of Plasmodium berghei. 1008 Mar 86

To determine whether the increased fatty acid beta-oxidation in the peroxisomes of diabetic rat liver is mediated by a common peroxisome proliferation mechanism, we measured the activation of long-chain (LC) and very long chain (VLC) fatty acids catalyzed by palmitoyl CoA ligase (PAL) and lignoceryl CoA ligase and oxidation of LC (palmitic acid) and VLC (lignoceric acid) fatty acids by isotopic methods. Immunoblot analysis of acyl-CoA oxidase (ACO), and Northern blot analysis of peroxisome proliferator-activated receptor (PPAR-alpha), ACO, and PAL were also performed. The PAL activity increased in peroxisomes and mitochondria from the liver of diabetic rats by 2.6-fold and 2.1 -fold, respectively. The lignoceroyl-CoA ligase activity increased by 2.6-fold in diabetic peroxisomes. Palmitic acid oxidation increased in the diabetic peroxisomes and mitochondria by 2.5-fold and 2.7-fold, respectively, while lignoceric acid oxidation increased by 2.0-fold in the peroxisomes. Immunoreactive ACO protein increased by 2-fold in the diabetic group. The mRNA levels for PPAR-alpha, ACO and PAL increased 2.9-, 2.8- and 1.6-fold, respectively, in the diabetic group. These results suggest that the increased supply of fatty acids to liver in diabetic state stimulates the expression of PPAR-alpha and its target genes responsible for the metabolism of fatty acids.
Mol Cell Biochem 1999 Apr
PMID:Increased peroxisomal fatty acid beta-oxidation and enhanced expression of peroxisome proliferator-activated receptor-alpha in diabetic rat liver. 1039 Nov 44

The pheromone response in the yeast Saccharomyces cerevisiae is mediated by a heterotrimeric G protein. The Gbetagamma subunit (a complex of Ste4p and Ste18p) is associated with both internal and plasma membranes, and a portion is not stably associated with either membrane fraction. Like Ras, Ste18p contains a farnesyl-directing CaaX box motif (C-terminal residues 107 to 110) and a cysteine residue (Cys 106) that is a potential site for palmitoylation. Mutant Ste18p containing serine at position 106 (mutation ste18-C106S) migrated more rapidly than wild-type Ste18p during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The electrophoretic mobility of wild-type Ste18p (but not the mutant Ste18p) was sensitive to hydroxylamine treatment, consistent with palmitoyl modification at Cys 106. Furthermore, immunoprecipitation of the Gbetagamma complex from cells cultured in the presence of [(3)H]palmitic acid resulted in two radioactive species on nonreducing SDS-PAGE gels, with molecular weights corresponding to Ggamma and Gbetagamma. Substitution of serine for either Cys 107 or Cys 106 resulted in the failure of Gbetagamma to associate with membranes. The Cys 107 substitution also resulted in reduced steady-state accumulation of Ste18p, suggesting that the stability of Ste18p requires modification at Cys 107. All of the mutant forms of Ste18p formed complexes with Ste4p, as assessed by coimmunoprecipitation. We conclude that tight membrane attachment of the wild-type Gbetagamma depends on palmitoylation at Cys 106 and prenylation at Cys 107 of Ste18p.
Mol Cell Biol 1999 Nov
PMID:Dual lipid modification of the yeast ggamma subunit Ste18p determines membrane localization of Gbetagamma. 1052 59

The human breast cancer cell line MCF7 does not express heart-type fatty acid binding protein (H-FABP), a marker protein for differentiated mammary gland. MCF7 cells transfected with the bovine H-FABP cDNA expressed the corresponding protein and were characterized by growth inhibition and lower tumorgenicity in nude mice [22]. By enzyme linked immunoassay we now determined the amount of bovine H-FABP in these cells as 638 +/- 80 ng/mg protein and used the transfected cells to study the role of H-FABP in fatty acid metabolism. Compared to control cells the uptake of radioactively labelled palmitic acid and oleic acid into MCF7 cells after 30 or 60 min was increased by 67% in H-FABP expressing transfectants, demonstrating a stimulatory role for this FABP-type in fatty acid metabolism. However, preferential targeting of [14C]oleic acid into neutral or phospholipid classes was not observed by the criterion of high performance thin layer chromatography followed by autoradiography. A reason for the modest increase of fatty acid uptake in H-FABP transfected MCF7 cells may be the basal expression of epidermal-type FABP, which was detected for the first time in these cells. It appears that the small amount of E-FABP expressed in MCF7 cells fulfils the need of the cells for a cytosolic fatty acid carrier under culture conditions and that even high concentrations of another FABP do only slightly increase the uptake due to limitations of fatty acid transport through the plasma membrane or of metabolism.
Mol Cell Biochem 1999 Sep
PMID:Fatty acid metabolism in human breast cancer cells (MCF7) transfected with heart-type fatty acid binding protein. 1054 50

Plasma from the Antarctic toothfish, Dissostichus mawsoni, a member of the advanced teleost Nototheniidae family, was analysed. Agarose gel electrophoresis showed a major diffuse anionic protein that bound [14C]palmitic acid but not 63Ni2+, and two more cationic proteins that bound 63Ni2+ but not palmitate. Oil Red O staining following cellulose acetate electrophoresis indicated that the palmitate binding protein was a lipoprotein. Two-dimensional electrophoresis showed that this palmitate binding band was composed of three proteins with M(r) of 11, 30, and 42 kDa, without any trace of material at approximately 65 kDa, the mass of albumin. N-terminal sequencing of the palmitate binding band gave a major sequence of DAAQPSQELR-, indicating a high degree of homology to apolipoprotein A-I (apo-AI), the major apolipoprotein of high density lipoprotein (HDL). N-terminal sequencing of the major nickel binding band produced a sequence with no homology to albumin. When ultracentrifugation was used to isolate the lipoproteins from Antarctic toothfish plasma, the palmitate binding protein was found solely in the lipoprotein fraction. In competitive binding experiments, added human albumin did not prevent palmitate binding to toothfish HDL. In conclusion, there is no evidence for albumin in Antarctic toothfish plasma and HDL assumes the role of fatty acid transport.
Comp Biochem Physiol B Biochem Mol Biol 1999 Oct
PMID:The Antarctic toothfish (Dissostichus mawsoni) lacks plasma albumin and utilises high density lipoprotein as its major palmitate binding protein. 1058 98

Disaturated phosphatidylcholine (DSPC) is the predominate phospholipid component of lung surfactant. In the alveolar type II cell, the cytidine diphosphocholine (CDP-choline) pathway is the major biosynthetic pathway for DSPC. To investigate the hypothesis that phosphocholine cytidylyltransferase (CT) is the rate-limiting enzyme in the CDP-choline pathway, rat alveolar type II cells or lung tumor-derived cell lines (A549 or H441) with type II cell features were transfected with CT complementary DNA (cDNA). Cell fractions were subsequently assayed for CT protein and activity, and cell rates of DSPC synthesis were determined. In all cases, cell CT protein and activity were increased after transfection with CT cDNA but not after control transfection. Rat type II cells, but not A549 or H441 cells, increased the rate of DSPC synthesis after transfection with CT cDNA. Exposure of type II cells transfected with CT cDNA to palmitic acid resulted in a further increase in CT protein and activity. Exposure to dexamethasone resulted in increased CT protein and activity and increased synthesis of DSPC. The results confirm that CT has a rate-limiting and regulatory role in the synthesis of type II cell DSPC, and raise possibilities for novel therapeutic interventions.
Am J Respir Cell Mol Biol 2000 Jan
PMID:Effect of phosphocholine cytidylyltransferase overexpression on phosphatidylcholine synthesis in alveolar type II cells and related cell lines. 1061 73

(Z)-11-Hexadecenyl acetate, the main pheromone component of Sesamia nonagrioides sex pheromone, is biosynthesized from palmitic acid by Delta(11)-desaturation followed by reduction and acetylation. Production of (Z)-11-hexadecenyl acetate is regulated by the Pheromone Biosynthesis Activating Neuropeptide (PBAN). Transformation of (Z)-11-hexadecen-1-ol into the corresponding acetate is a target step for PBAN in the regulation of this biosynthetic sequence, thus being the first example of a PBAN-activated acetylation. The production of the minor component (Z)-11-hexadecenal is also stimulated by PBAN. The usefulness of pentafluorobenzyloxime-derivatives for the analysis of aldehyde pheromone constituents by gas chromatography coupled to mass spectrometry is also reported.
Insect Biochem Mol Biol 2000 Jun
PMID:Control of the biosynthetic pathway of Sesamia nonagrioides sex pheromone by the pheromone biosynthesis activating neuropeptide. 1080 36

Previous studies have shown that aldosterone treatment of amphibian epithelial cells results not only in stimulation of Na(+) absorption but also in changes in phospholipid composition which are necessary for the mineralocorticoid action of aldosterone. The present study was designed to investigate the effect of aldosterone on phospholipids of mammalian epithelia. Phospholipid and fatty acid composition was examined in colonic epithelium (mineralocorticoid target tissue) and thymus (non-mineralocorticoid but glucocorticoid target tissue) of rats which had received aldosterone or vehicle by a miniosmotic pump for 7 days. Aldosterone increased the mass of colonic phospholipids relative to cellular proteins with concomitant changes in the percentage distribution of fatty acids, whereas the relative distribution of membrane phospholipds was not changed. Phosphatidylcholine increased the content of polyunsaturated and decreased that of monounsaturated fatty acids, which predominantly reflected the accretion of arachidonic and a decrease in oleic and palmitoleic acids. Within the phosphatidylethanolamine subclass, pretreatment of rats with aldosterone decreased the content of monounsaturated fatty acids (predominantly oleic and palmitoleic acid) and of n-3 fatty acids, and increased the content of saturated fatty acids (palmitic acid). The saturated-to-nonsaturated fatty acid ratio also significantly increased after aldosterone treatment. No changes in thymic phospholipids were seen. The results are consistent with the contention that aldosterone specifically modulates phospholipid concentration and metabolism in mineralocorticoid target tissue. The changes in phospholipid content and its fatty acid composition during the fully developed effect of aldosterone may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.
J Steroid Biochem Mol Biol 2000 May
PMID:Aldosterone alters the phospholipid composition of rat colonocytes. 1082 20

Mice with surfactant protein (SP)-D deficiency have three to four times more surfactant lipids in air spaces and lung tissue than control mice. We measured multiple aspects of surfactant metabolism and function to identify abnormalities resulting from SP-D deficiency. Relative to saturated phosphatidylcholine (Sat PC), SP-A and SP-C were decreased in the alveolar surfactant and the large-aggregate surfactant fraction. Although large-aggregate surfactant from SP-D gene-targeted [(-/-)] mice converted to small-aggregate surfactant more rapidly, surface tension values were comparable to values for surfactant from SP-D wild-type [(+/+)] mice. (125)I-SP-D was cleared with a half-life of 7 h from SP-D(-/-) mice vs. 13 h in SP-D(+/+) mice. Although initial incorporation and secretion rates for [(3)H]palmitic acid and [(14)C]choline into Sat PC were similar, the labeled Sat PC was lost from the lungs of SP-D(+/+) mice more rapidly than from SP-D(-/-) mice. Clearance rates of intratracheal [(3)H]dipalmitoylphosphatidylcholine were used to estimate net clearances of Sat PC, which were approximately threefold higher for alveolar and total lung Sat PC in SP-D(-/-) mice than in SP-D(+/+) mice. SP-D deficiency results in multiple abnormalities in surfactant forms and metabolism that cannot be attributed to a single mechanism.
Am J Physiol Lung Cell Mol Physiol 2000 Sep
PMID:Surfactant metabolism in SP-D gene-targeted mice. 1095 21


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