Disease relevance of tunicamycin

• The replication of vesicular stomatitis virus (VSV) is inhibited by tunicamycin (TM), an antibiotic that blocks the formation of N-acetylglucosaminelipid intermediates [1].
• Furthermore, mice lacking GADD34-directed eIF2alpha dephosphorylation, like CHOP(-/-) mice, are resistant to renal toxicity of the ER stress-inducing drug tunicamycin [2].
• It entailed exposing mice with defined chop genotypes to a single sublethal intraperitoneal injection of tunicamycin and resulted in a severe illness characterized by transient renal insufficiency [3].
• Treatment of human SH-SY5Y neuroblastoma cells with tunicamycin, an inhibitor of protein glycosylation, rapidly induced the expression of target genes of the unfolded protein response [4].
• Deletion of COD1 also impaired ER function, causing constitutive activation of the unfolded protein response, hypersensitivity to the glycosylation inhibitor tunicamycin, and synthetic lethality with deletion of the unfolded protein response regulator HAC1 [5].

Psychiatry related information on tunicamycin

• An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease [6].
• Results of biosynthetic labeling of BF0.3, 615.2, and Id 150 in the presence and absence of tunicamycin suggest that the difference in m.w. and charge observed between alpha m and alpha s can be attributed to differences in primary amino acid structure rather than different degrees of glycosylation [7].

High impact information on tunicamycin

• TGF-beta has little effect on the rate of overall protein synthesis, but the increase it induces in EGF binding can be completely inhibited by cycloheximide and tunicamycin [8].
• Neither N- nor O-glycosidically linked carbohydrates are involved in the transport defect of the mutant HA, because tunicamycin, an inhibitor of N-type glycosylation, has no effect, and O-type glycosylation takes place in the Golgi organelle [9].
• An 81 kd species is only found intracellularly when growing oocytes are cultured in the presence of tunicamycin [10].
• The synthesis of glycoproteins and inhibition of protein glycosylation by tunicamycin were examined during development of preimplantation mouse embryos and trophoblast adhesion [11].
• Glycoprotein synthesis and inhibition of glycosylation by tunicamycin in preimplantation mouse embryos: compaction and trophoblast adhesion [11].

Chemical compound and disease context of tunicamycin

• Exposure to glucosamine (1 mg/ml) or tunicamycin (0.2 to 0.4 micrograms/ml) induces a marked pigment loss within melanoma cells in vitro with a decrease in their grown curves [12].
• The glucose-regulated proteins (GRPs) are induced by chemical agents that disrupt protein trafficking in the endoplasmic reticulum such as tunicamycin and A23187 and by hypoxia [13].
• The glycosylated and nonglycosylated GCAPs, synthesized by butyrate-treated choriocarcinoma cells in the absence or presence of tunicamycin, respectively, were similarly inhibited by L-leucine or EDTA [14].
• The shedding of 2 tumor-specific glycoprotein antigens from human melanoma cells into spent culture medium was selectively inhibited by nontoxic doses (0.5 microgram/ml) of tunicamycin, an inhibitor of N-asparagine-linked glycosylation [15].
• Therefore, we examined the effect of tunicamycin (TM), an inhibitor of asparagine-linked glycosylation and ganglioside biosynthesis, on the expression of Hh-1 determinants in H-2b/Hh-1b lymphomas [16].

Biological context of tunicamycin

• Tunicamycin specifically inhibits glycosylation of asparaginyl residues of glycoproteins [11].
• Here we report that intraocular injection of tunicamycin produces a photoreceptor-specific degeneration characterized by progressive shortening of rod outer segment, decreased membrane assembly, and eventual photoreceptor cell death [17].
• The inhibitory effects of interferon on virus multiplication and cell growth are significantly enhanced by treatment with tunicamycin [18].
• The in vitro phenotype of sec53 could be mimicked by isolating rough microsomes from wild-type cells that had been grown for 1 h in the presence of tunicamycin [19].
• The glycosylation inhibitor tunicamycin has little effect on either regeneration kinetics or the complement of flagellar peptides as seen in SDS acrylamide gels, but tunicamycin totally inhibits incorporation of exogenously supplied [14C]xylose into flagellar glycoproteins [20].

Anatomical context of tunicamycin

• Using tunicamycin, we have investigated the role of glycosylation in the biosynthesis, processing and turnover of CSP, the major cell surface glycoprotein of chick embryo fibroblasts (CEF) [21].
• Role of carbohydrates in protein secretion and turnover: effects of tunicamycin on the major cell surface glycoprotein of chick embryo fibroblasts [21].
• We had shown previously that the viral glycoprotein (G) synthesized in cells treated with TM is not glycosylated and is not found on the outer surface of the cell plasma membrane [1].
• Incorporation of 3H-mannose into blastocysts was inhibited by 80%, but that of 3H-glucosamine and 3H-leucine by only 28 and 18%, respectively, in the presence of 1.0 microgram/ml tunicamycin [11].
• We have reported that tunicamycin can disrupt the normal assembly of rod outer segment membranes in vitro without significantly inhibiting the biosynthesis or intracellular transport of opsin [17].

Associations of tunicamycin with other chemical compounds

• To examine this issue, we have directly explored the binding of calnexin to both Ii truncation mutants lacking the typical sites of N-glycosylation or Ii produced in cells treated with tunicamycin to prevent glycan addition [22].
• Pulse-labeling and inhibition of glycosylation by tunicamycin show that the electrophoretic polymorphism is of polypeptide origin, whereas N-linked oligosaccharrides and sialic acid residues contribute to the microheterogeneity of the profile [23].
• Removal of sialic acids with neuraminidase or inhibition of glycosylation with tunicamycin reduced the microheterogeneity of both DR subunits [24].
• The acetaldehyde-stimulated mitochondrial cholesterol content was preceded by increased levels of endoplasmic reticulum (ER)-responsive gene GADD153 and transcription factor sterol regulatory element-binding protein 1 and mimicked by the ER stress-inducing agents tunicamycin and homocysteine [25].
• The glycosylation of GPIIb-IIIa was examined in megakaryocytes by metabolic labeling in the presence of tunicamycin, monensin, or treatment with endoglycosidase H [26].

Gene context of tunicamycin

• Over-expression of a dominant-negative form of Ire1 blocks the induction of GRP78/BiP and CHOP in response to the ER stress induced by tunicamycin treatment [27].
• Knockdown of endogenous ATF4 or CHOP expression dramatically repressed tunicamycin-induced TRB3 induction [28].
• In many, but not in all cases, CD44 does not bind HA unless it is stimulated by phorbol esters, activated by agonistic anti-CD44 antibody, or deglycosylated (e.g., by tunicamycin) [29].
• Enforced overexpression of cyclin D1 in tunicamycin-treated cells maintained cyclin D- and E-dependent kinase activities and kept cells in cycle in the face of a fully activated UPR [30].
• By using N-glycosidase F, tunicamycin, and specific antibodies produced in both chicken and rabbit, we demonstrate that PlGF, derived from transfected COS-1 cells, is actually N-glycosylated and secreted into the medium [31].

Analytical, diagnostic and therapeutic context of tunicamycin

• Tunicamycin had only a slight effect on the initial times and rates of CSP appearance on the cell surface; some apparent intracellular redistribution of CSP was detected by immunofluorescence [21].
• Periodate treatment followed by binding analysis and immunoprecipitation experiments using tunicamycin-treated cells indicated that carbohydrate is necessary for CT antigen expression [32].
• After treatment with either neuraminidase or tunicamycin, the DR light chains, but not the heavy chains, were still structurally polymorphic [24].
• Disruption of N-linked glycosylation of tPA by either site-directed mutagenesis or tunicamycin treatment resulted in reduced levels of secretion and increased association with BiP [33].
• Microarray analysis of gene expression changes during tunicamycin-induced apoptosis revealed that the Bcl-2 homology domain 3-only family member, Bcl-2 binding component 3/p53 upregulated modulator of apoptosis (Bbc3/PUMA), was the most strongly induced pro-apoptotic gene [4].

References