Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the class II region of the major histocompatibility complex (MHC(, four genes implicated in MHC class I-mediated antigen processing have been described. Two genes (TAP1 and TAP2) code for multimembrane-spanning ATP-binding transporter proteins and two genes (LMP2 and LMP7) code for subunits of the proteasome. While TAP1 and TAP2 have been shown to transport antigenic peptides from the cytosol into the endoplasmic reticulum, where the peptides associate with MHC class I molecules, the role of LMP2/7 in antigen presentation is less clear. Using antigen processing mutant T2 cells that lack TAP1/2 and LMP2/7 genes, it was recently shown that expression of TAP1/2 alone was sufficient for processing and presentation of the influenza matrix protein M1 as well as the minor histocompatibility antigen HA-2 by HLA-A2. To understand if presentation of a broader range of viral antigens occurs in the absence of LMP2/7, we transfected T2 cells with TAP1, TAP2 and either of the H-2Kb, Db or Kd genes and tested their ability to present vesicular stomatitis vires and influenza virus antigens to virus-specific cytotoxic T lymphocytes. We found that T2 cells, expressing TAP1/2 gene products, presented all tested viral antigens restricted through either the H-2Kb, Db or Kd class I molecules. We conclude that the proteasome subunits LMP2/7 as well as other gene products in the MHC class II region, except from TAP1/2, are not generally necessary for presentation of a broader panel of viral antigens to cytotoxic T cells. However, the present results do not exclude that LMP2/7 in a more subtle way may, or in rare cases completely, affect processing of antigen for presentation by MHC class I molecules.
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PMID:Presentation of viral antigens restricted by H-2Kb, Db or Kd in proteasome subunit LMP2- and LMP7-deficient cells. 805 44

Several red cell storage properties were evaluated following phototreatment with methylene blue (MB) under conditions that inactivated > or = 6 log10 of added vesicular stomatitis virus. Red cell 2,3 DPG levels were similar to untreated controls throughout conventional 42-day storage at 4 degrees C. Plasma hemoglobin levels were elevated approximately twofold in MB-phototreated samples, and morphology scores were 5 percent lower after 42-day storage. ATP levels declined 30 percent in phototreated samples and in a control sample containing MB and not exposed to light. Lipid peroxidation was not observed in treated or control cells, nor were differences observed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis of ghost membranes derived from phototreated and control samples. Phototreated cells exhibited enhanced ion permeability; sodium and potassium levels approached equilibrium with the suspending medium within 4 to 7 days after treatment. Direct agglutination tests using rabbit anti-human IgG or rabbit anti-human serum albumin on MB-phototreated cells indicated that serum proteins had absorbed to the surface of treated red cells. Plasma depletion by washing red cells prior to phototreatment did not prevent protein binding upon subsequent addition of untreated autologous or group AB plasma. To a much smaller extent, phototreatment of plasma resulted in IgG association with untreated red cells. The addition of glutathione to red cell suspensions prevented IgG binding to phototreated red cells but did not prevent enhanced ion permeability. Taken together, these data suggest that the red cell surface is altered by virucidal MB phototreatment of vesicular stomatitis virus.
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PMID:Red cell alterations associated with virucidal methylene blue phototreatment. 838 Sep 45

Using the glycoprotein of the tsO45 mutant of vesicular stomatitis virus (VSV-G) as a marker, we have developed a system capable of measuring vesicular transport from the endoplasmic reticulum (ER) to the trans Golgi network (TGN) in vitro. Movement from the ER to the cis Golgi compartment was assessed by the conversion of VSV-G from a totally endoglycosidase D (endo D)-resistant form to a species containing one endo D-resistant and one endo D-sensitive oligosaccharide (GD1). Similarly, delivery to the medial cisternae was measured by the appearance of the completely endo D-sensitive form of VSV-G (GD2) or by the acquisition of complete resistance to endoglycosidase H (endo H) (GHr) and delivery to the TGN by the appearance of an endo H-resistant form of VSV-G which was sensitive to digestion with neuraminidase and subsequently beta-galactosidase (GHt). Movement between each sequential compartment required ATP and soluble proteins (cytosol) and was inhibited by nonhydrolyzable analogues of GTP and by an antibody toward the N-ethylmaleimide-sensitive factor NSF. In contrast, fractionation of the cytosol by ammonium sulfate precipitation indicated that distinct proteins were required for movement between successive compartments. Similarly, inclusion of a mutant form of the small molecular weight GTP-binding protein rab1A inhibited movement between the ER and cis Golgi, and between the cis and medial cisternae, but did not affect transport from the medial Golgi to the TGN. Conversely, the protein kinase inhibitor staurosporine prevented movement between the medial Golgi and the TGN but did not influence transport between the ER and early Golgi compartments. This study provides the first demonstration that vesicular transport between the ER and TGN can be reconstituted in a cytosol-dependent fashion in vitro, allowing a direct analysis of the roles of individual components in multiple transport events.
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PMID:Differential inhibition of multiple vesicular transport steps between the endoplasmic reticulum and trans Golgi network. 838 97

Using influenza hemagglutinin (HA0) and vesicular stomatitis virus G protein as model proteins, we have analyzed the effects of dithiothreitol (DTT) on conformational maturation and transport of glycoproteins in the secretory pathway of living cells. While DTT caused reduction of folding intermediates and misfolded proteins in the endoplasmic reticulum (ER), it did not affect molecules that had already acquired a mature trimeric conformation, whether present in the ER or elsewhere. The conversion to DTT resistance was therefore a pre-Golgi event. Reduction of folding intermediates was dependent on the intactness of the ER and on metabolic energy, suggesting cooperativity between DTT and ER folding factors. DTT did not inhibit most cellular functions, including ATP synthesis and protein transport within the secretory pathway. The results established DTT as an effective tool for analyzing the folding and compartmental distribution of proteins with disulfide bonds.
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PMID:Membrane glycoprotein folding, oligomerization and intracellular transport: effects of dithiothreitol in living cells. 849 Dec 3

We have developed a system that recreates in vitro the generation of post-Golgi vesicles from an isolated Golgi fraction prepared from vesicular stomatitis virus- or influenza virus-infected Madin-Darby canine kidney or HepG2 cells. In this system, vesicle generation is temperature- and ATP-dependent and requires a supply of cytosolic proteins, including an N-ethylmaleimide-sensitive factor distinct from NSF. Cytosolic proteins obtained from yeast were as effective as mammalian cytosolic proteins in supporting vesicle formation and had the same requirements. The vesicles produced (50-80 nm in diameter) are depleted of the trans Golgi marker sialyltransferase, contain the viral glycoprotein molecules with their cytoplasmic tails exposed, and do not show an easily recognizable protein coat. Vesicle generation was inhibited by brefeldin A, which indicates that it requires the activation of an Arf-like GTP-binding protein that promotes assembly of a vesicle coat. Vesicles formed in the presence of the nonhydrolyzable GTP analogue guanosine 5'-3-O-(thio)triphosphate retained a nonclathrin protein coat resembling that of COP-coated vesicles, and sedimented more rapidly in a sucrose gradient than the uncoated ones generated in its absence. This indicates that GTP hydrolysis is not required for vesicle generation but that it is for vesicle uncoating. The activity of a Golgi-associated protein kinase C (PKC) was found to be necessary for the release of post-Golgi vesicles, as indicated by the capacity of a variety of inhibitors and antibodies to PKC to suppress it, as well as by the stimulatory effect of the PKC activator 12-O-tetradecanoylphorbol-13-acetate.
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PMID:The in vitro generation of post-Golgi vesicles carrying viral envelope glycoproteins requires an ARF-like GTP-binding protein and a protein kinase C associated with the Golgi apparatus. 866 71

During the course of screening studies to identify inhibitors of intracellular protein trafficking, we isolated efrapeptins as active principles. These compounds arrested syncytium formation (SF) and cytopathic effect (CPE) in Newcastle disease virus (NDV)- and vesicular stomatitis virus (VSV)-infected BHK cells, respectively, without profoundly affecting glycoprotein synthesis. Efrapeptins blocked cell surface expression of NDV-HN and VSV-G glycoproteins, but did not suppress intoxication by ricin or diphtheria toxin even after prolonged pretreatment. Efrapeptins are inhibitors of F-ATPase, or ATP synthase, but their inhibitory effect on SF and CPE was independent of the amount of intracellular ATP.
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PMID:Efrapeptins block exocytic but not endocytic trafficking of proteins. 888 13

We have recently described a system that recreates in vitro the generation of post-Golgi vesicles from purified Golgi fractions obtained from virus-infected MDCK cells in which the vesicular stomatitis virus-G envelope glycoprotein had been allowed to accumulate in vivo in the TGN. Vesicle formation, monitored by the release of the viral glycoprotein, was shown to require the activation of a GTP-binding ADP ribosylation factor (ARF) protein that promotes the assembly of a vesicle coat in the TGN, and to be regulated by a Golgi-associated protein kinase C (PKC)-like activity. We have now been able to dissect the process of post-Golgi vesicle generation into two sequential stages, one of coat assembly and bud formation, and another of vesicle scission, neither of which requires an ATP supply. The first stage can occur at 20 degrees C, and includes the GTP-dependent activation of the ARF protein, which can be effected by the nonhydrolyzable nucleotide analogue GTP gamma S, whereas the second stage is nucleotide independent and can only occur at a higher temperature of incubation. Cytosolic proteins are required for the vesicle scission step and they cannot be replaced by palmitoyl CoA, which is known to promote, by itself, scission of the coatomer-coated vesicles that mediate intra-Golgi transport. We have found that PKC inhibitors prevented vesicle generation, even when this was sustained by GTP gamma S and ATP levels reduced far below the K(m) of PKC. The inhibitors suppressed vesicle scission without preventing coat assembly, yet to exert their effect, they had to be added before coat assembly took place. This indicates that a target of the putative PKC is activated during the bud assembly stage of vesicle formation, but only acts during the phase of vesicle release. The behavior of the PKC target during vesicle formation resembles that of phospholipase D (PLD), a Golgi-associated enzyme that has been shown to be activated by PKC, even in the absence of the latter's phosphorylating activity. We therefore propose that during coat assembly, PKC activates a PLD that, during the incubation at 37 degrees C, promotes vesicle scission by remodeling the phospholipid bilayer and severing connections between the vesicles and the donor membrane.
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PMID:The production of post-Golgi vesicles requires a protein kinase C-like molecule, but not its phosphorylating activity. 889 94

The nonapeptide leucinostatin A (LSA) inhibited syncytium formation without profoundly affecting HN glycoprotein synthesis in Newcastle disease virus (NDV)-infected BHK cells. At similar doses of LSA, cytopathic effect and infectious virus production were suppressed in vesicular stomatitis virus (VSV)-infected BHK cells. Blockade by LSA of cell surface expression of NDV-HN and VSV-G glycoproteins was demonstrated, accompanied by intracellular accumulation of these virus glycoproteins. LSA acts as an inhibitor of mitochondrial F-type H(+)-translocating ATPase, a key enzyme in the generation of ATP, but its action against cell surface expression of virus glycoproteins was independent of the depletion of intracellular ATP. LSA also acts as an ionophore, but its action on intoxication by ricin and diphtheria toxin was different from that of monensin. This novel action of LSA is expected to be useful in investigation of the mechanism of intracellular trafficking of proteins.
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PMID:Novel blockade of cell surface expression of virus glycoproteins by leucinostatin A. 898 41

Previous studies with methylene blue (MB) in red cell suspensions have demonstrated that extracellular, but not intracellular, virus can be readily photoinactivated. To test if the resistance of intracellular virus to inactivation is related to the permanent positive charge of the phenothiazine, a series of uncharged phenothiazine dyes, methylene violet (MV), monodemethylated MV and didemethylated MV, were studied. Values of the sensitivity of intracellular relative to extracellular vesicular stomatitis virus (VSV) inactivation for the three dyes (D10 extracellular/D10 intracellular) in buffer were 1.0, 0.60 and 0.33, respectively. In contrast, intracellular virus was resistant to inactivation with MB, with a D10 extracellular/D10 intracellular of 0.05 in buffer. Because virucidal activity of MV was inhibited by the presence of plasma, the red cells (30% hematocrit) were repeatedly washed prior to photoinactivation and storage. Under conditions where MB and MV inactivated approximately 5 log10 of extracellular VSV, intracellular VSV was inactivated by more than 4 log10 with MV compared to 0.88 log10 with MB. These phototreatment conditions did not significantly affect red cell morphology, extracellular pH, ATP or 2,3-diphosphoglycerol levels during 42 days of 1-6 degrees C storage. There was enhanced potassium efflux and hemolysis over values obtained from untreated control; the extent of change from controls was comparable for each phototreatment. These results indicate that the uncharged phenothiazine dye, MV, can inactivate both intracellular and extracellular virus yet exhibit similar in vitro red cell storage properties as MB phototreatment.
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PMID:Comparison of methylene blue and methylene violet for photoinactivation of intracellular and extracellular virus in red cell suspensions. 907 30

GRP94, the endoplasmic reticulum Hsp90 paralog, binds a diverse array of peptides, a subset of which are suitable for assembly onto nascent MHC class I molecules. At present, the mechanism, site, and regulation of peptide binding to GRP94 are unknown. Using VSV8, the immunodominant peptide epitope of the vesicular stomatitis virus, and native, purified GRP94, we have investigated GRP94-peptide complex formation. The formation of stable GRP94-VSV8 complexes was slow; competition studies demonstrated that peptide binding to GRP94 was specific. VSV8 binding to GRP94 was stimulated 2-fold or 4-fold, respectively, following chemical denaturation/renaturation or transient heat shock. The activation of GRP94-peptide binding occurred coincident with a stable, tertiary conformational change, as identified by tryptophan fluorescence and proteolysis studies. Analysis of GRP94 secondary structure by circular dichroism spectroscopy indicated an identical alpha-helical content for the native, chemically denatured/renatured, and heat-shocked forms of GRP94. Through use of the environment-sensitive fluorophores acrylodan and Nile Red, it was observed that the activation of peptide binding was accompanied by enhanced peptide and solvent accessibility to a hydrophobic binding site(s). Peptide binding to native or activated GRP94 was identical in the presence or absence of ATP or ADP. These results are discussed with respect to a model in which peptide binding to GRP94 occurs within a hydrophobic binding pocket whose accessibility is conformationally regulated in an adenine nucleotide-independent manner.
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PMID:Structural transitions accompanying the activation of peptide binding to the endoplasmic reticulum Hsp90 chaperone GRP94. 954 57


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