Disease relevance of Vamp8

• Thus, the carcinogen EDB caused substantial DNA damage at doses far below those required to show other biochemical effects or frank liver toxicity [1].

High impact information on Vamp8

• EDA+ FN was significantly more potent than EDA- FN in promoting cell spreading and cell migration, irrespective of the presence or absence of a second alternatively spliced segment, EDB [2].
• In addition, RRC was very rich in proteins previously shown to be associated with recycling endosomes, such as rab 11, cellubrevin, and endobrevin, but relatively poor in early endosome antigen 1 [3].
• The major DNA adduct formed from the carcinogen ethylene dibromide (1,2-dibromoethane, EDB) is S-[2-(N7-guanyl)ethyl]glutathione, resulting from the reaction of guanyl residues with the half-mustard S-(2-bromoethyl)glutathione, which is generated by glutathione S-transferase-catalyzed conjugation of EDB with glutathione [4].
• Treatment of isolated rat hepatocytes with diethylmaleate decreased covalent binding of EDB to DNA, but treatment with 1-phenylimidazole did not, consistent with the view that conjugative metabolism is of greater importance than oxidation with regard to DNA binding [4].
• The gamma-glutamyl transpeptidase inhibitor AT-125 [L-(alpha-(5S)-alpha-amino-S-chloro-4,5-dihydro-5-isoxazoleacetic acid] did not affect the level of EDB bound to DNA by glutathione-fortified rat kidney homogenates or bound to liver or kidney DNA in vivo [4].

Biological context of Vamp8

• In addition, syntaxin 4 and the v-SNARE endobrevin/VAMP-8 localize to this sub-tight junctional domain, which suggests that this is a region of preferred vesicle exocytosis [5].
• Syntaxin 2 and endobrevin are required for the terminal step of cytokinesis in mammalian cells [6].
• The DNA damage produced by EDB (600 microM) was also inhibited by pretreatment of testicular cells with DEM (1 mM) [7].
• This suggests that the mixed-function oxidase pathway of metabolism is the primary route of clearance of EDB and that inhibition of cytochrome P450-mediated oxidation led to a more extensive tissue distribution of the parent compound [8].
• At 13 weeks, rats and mice showed severe necrosis and atrophy of the olfactory epithelium in the nasal cavity after inhalation of 5 or 25 ppm DBCP and 75 ppm EDB [9].

Anatomical context of Vamp8

• Endobrevin/VAMP-8 is an R-SNARE localized to endosomes, but it is unknown in which intracellular fusion step it operates [10].
• Using subcellular fractionation and quantitative immunogold electron microscopy, we found that endobrevin/VAMP-8 is present on all membranes known to communicate with early endosomes, including the plasma membrane, clathrin-coated pits, late endosomes, and membranes of the trans-Golgi network [10].
• Here we show that VAMP8/endobrevin cycles through the apical but not through the basolateral plasma membrane [11].
• This asymmetry in localization and cycling behavior suggests that VAMP8/endobrevin may play a role in apical endosomal trafficking in polarized epithelium cells [11].
• In this study we have examined EDB-induced unscheduled DNA synthesis (UDS) in F-344 rat pachytene spermatocytes and hepatocytes [8].

Associations of Vamp8 with chemical compounds

• Similarly, it was shown that 1,2-dibromoethane (EDB), a structurally related halogenated alkane, produced DNA damage in isolated testicular cells in both a time- (0-60 min) and concentration- (0-600 microM) dependent fashion [7].
• We have shown that the R-SNARE (arginine-containing SNARE) protein VAMP (vesicle-associated membrane protein) 7 is necessary for heterotypic fusion between late endosomes and lysosomes, whereas a different R-SNARE, VAMP 8 is required for homotypic fusion of late endosomes [12].
• EDB is biotransformed either by cytochrome P450-dependent oxidation, leading to the formation of bromoacetaldehyde, or by enzyme-catalyzed conjugation with glutathione, giving rise to reactive half-sulfur mustard compounds and their derivatives [8].
• Treatment of rats with 175 mg metyrapone/kg (an inhibitor of hepatic mixed-function oxidases) 1 h prior to administration of EDB in vivo had no effect on EDB-induced UDS in hepatocytes, but led to a positive UDS response to EDB in spermatocytes in vivo [8].
• Phenobarbitone (PB) treatment of rats together with low dose of EDB during 2 weeks prevented the enzyme activity elevation and attenuated the DNA synthesis [13].

Physical interactions of Vamp8

• Co-immunoprecipitation demonstrated separate syntaxin 7 complexes with either VAMP7 or VAMP8 in solubilized rat liver membranes [14].

Other interactions of Vamp8

• Cognate SNARE complexes of syntaxin3 with SNAP-23 and VAMP-8 were enriched in rafts, whereas Munc18-2/syntaxin3 complexes were excluded [15].

Analytical, diagnostic and therapeutic context of Vamp8

• Using immunoprecipitation methods, syntaxins 3 and 4 were seen to interact with VAMP-8 and SNAP-23 at the APM, respectively [16].
• Indirect immunofluorescence microscopy establishes that endobrevin is primarily associated with the perinuclear vesicular structures of the early endocytic compartment [17].
• Reversed-phase HPLC analysis of pronase digest of the albumin obtained from in vitro studies indicated formation of several amino acid adducts of EDB and/or its metabolites [18].
• Single i.p. injections of EDB or DBCP (40 mg/kg, approximately one-half of the acute, i.p. LD50 values) were without effect on serum GPT and GOT activities, BUN concentration or the accumulations of PAH and TEA in male rats when measured 24, 48 or 96 h after treatment, except that PAH accumulation was reduced at 96 h [19].

References