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Mass Spectrometric Analysis
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Considerable work has been reported in the characterization of tunicamycin and streptovirudin, two similar nucleoside antibiotic complexes that inhibit the transfer of N-acetylglucosamine from UDP-GlcNAc to intermediates used in the synthesis of complex lipids. Previously reported were four major components and several decomposition products [212—214]. More recently, improved chromatography has enabled the separation and identification of six additional components [215]. The identifications were aided by EI mass spectra that provided molecular ions and characteristic fragments. The tunicamycin components contain uracil; the streptovirudins contain uracil and dihydrouracil. Molecular weights and elemental compositions of the streptovirudins were obtained by FD [216]. Sensitive GC-MS methods using EI were used to detect uracil and dihydrouracil, as well as determine the fatty acid components after acid hydrolysis [217]. Some of the streptovirudins are identical to tunicamycin components. Another uracil antibiotic, nikko-mycin, was identified from the EI spectra of the derivatized nucleoside and hydrolysis products [218].
Intracellular Maturation of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Erik Fries, E. Mathilda Sjöberg
The formation of N-linked carbohydrates can be inhibited by the addition of the antibiotic tunicamycin.68 Use of this compound has made it possible to study the role of N-linked carbohydrates in secretion. When Hep G2 cells or hepatocytes are treated with tunicamycin, the secretion of some, but not all, proteins is impaired.66,67,69,70 In another type of cell, it has been shown that a protein’s sensitivity to tunicamycin treatment is correlated to its binding to BiP,30 suggesting an effect of the glycan moiety on the conformation of the polypeptide. A number of compounds have been discovered which inhibit specific hydrolases of the N-glycosylation pathway.68 Thus, for example, deoxynojirimycin inhibits the ER enzymes which remove the glucoses. When Hep G2 cells are incubated with this compound, the secretion of some proteins is inhibited.69,71 The mechanism of this differential retention of proteins with incompletely processed oligosaccharides is unknown. Deoxymannojirimycin, on the other hand, inhibits the Golgi enzymes that reduce the number of mannose residues down to five; in the presence of this compound, the transport rates are unaffected.72,73
Current Concepts of Implantation and Decidualization
Published in Gabor Huszar, The Physiology and Biochemistry of the Uterus in Pregnancy and Labor, 2020
The importance of N-linked glycoproteins was provisionally reaffirmed by demonstrating the irreversible inhibition of trophoblast adhesion, outgrowth, and Con A binding in blastocysts incubated in the presence of tunicamycin which interferes with protein glycosylation.45,70 The incorporation of mannose was preferentially reduced (80%) compared to glucosamine (28%) and leucine (18%); the synthesis of the carbohydrate-deficient proteins was essentially normal. The results obtained by others71 fail to confirm the tunicamycin effect. Questions have also been raised about the significance of the reduction in protein synthesis which is accompanied by a decrease in membrane-bound ribosomes.72 However, the amounts of cycloheximide which cause the same reduction in total protein synthesis, as does tunicamycin (18%), do not affect the adhesion and outgrowth of treated blastocysts.45 The possibility of tunicamycin cytotoxicity should always be evaluated. The issue deserves further investigation which will include the use of specific proteases and glycosidases to separate the role of glycosylation from protein synthesis in trophoblast adhesion and outgrowth.
Emerging Human Coronavirus Infections (SARS, MERS, and COVID-19): Where They Are Leading Us
Published in International Reviews of Immunology, 2021
The RBD of the S1 protein resides between its 303 and 537 residues [258]. However, further study has specified that the amino acids 1 to 510 of the SARS-CoV S1 glycoprotein comprise a unique domain, which contains the receptor-binding site (AAs 270 to 510) analogous to the S1 subunit of the S protein of other CoVs [259]. The more specific study has established now the recognition region in S1 exists within a 193 AA sequence (residues 318–510), and smaller fragments (expressing residues 327–510 or 318–490) do not bind ACE2 [260]. The CoV S glycoproteins are decorated with an extensive glycan shield made up of 100 N-linked oligosaccharides [261,262]. These glycans provide stability to S glycoprotein during biogenesis as the glycosylation inhibition with tunicamycin causes the S glycoprotein lacking virion production [263]. Also, the glycation of S glycoprotein masks their epitope region, which helps in the immune evasion [261,262,264].
(-)-Clausenamide alleviated ER stress and apoptosis induced by OGD/R in primary neuron cultures
Published in Neurological Research, 2020
Fei Wu, Rumin Zhang, Qizhen Feng, Hongju Cheng, Jianjun Xue, Jing Chen
Clausenamide was isolated from the aqueous extract of Clausena lansium (lour) Skeels, a Chinese traditional medicine which abounds in the South of China. (-)-Clausenamide (3-hydroxy-4-phenyl-5a-hydroxybenzylN-methyl-g-lactam, (-)-Clau, Figure 1), a partial chemical structure of which is similar to the pharmacophore of piracetam, a nootropic drug developed in Europe. (-)-Clau shows strong hydrophobicity because of two hydrophobic phenyl rings, making it easy to reach central nervous system through blood-brain-barrier. The chemical compound (-)-Clau could been artificially synthesized [11], and a US patent protecting the technology of its chemical synthesis has been granted (US Patent No. 6,787,564 B2) [12]. It was demonstrated that (-)-Clau could antagonize Aβ-induced neurotoxicity in differentiated PC12 cells [12], and potentiated basal synaptic transmission, improved learning and memory in amnesia animal models [11,13,14]. Tunicamycin (TM), an antibiotic, which is reported to be a glycosylation blocker, could obstruct glycoprotein synthesis and finally induce ERS [15,16]. Here, TM was applied as the ERS inducer. The present study showed that (-)-Clau could alleviate OGD/R-induced ERS and neural apoptosis, while TM could counteract the inhibitory effect of (-)-Clau, indicating that (-)-Clau may have a therapeutic potential to protect neurons from ischemia/reperfusion injury by attenuating ERS.
Endoplasmic reticulum stress in the livers of BDNF heterozygous knockout mice
Published in Archives of Physiology and Biochemistry, 2019
Selma Cırrık, Gulay Hacioglu, İsmail Abidin, Selcen Aydın-Abidin, Tevfik Noyan
Tunicamycin (Tm, Sigma-Aldrich, Catalog number; T7765, St. Louis, MO, USA) is an ER stress-inducing agent which inhibits N-glycosylation in ER (Moslehi et al.2017). In the present study, ER stress was induced by a single dose of Tm injection (0.5 mg/kg; intraperitoneally) in WT + Tm and BDNF(±)+Tm groups. Intraperitoneal saline (as vehicle) was injected in WT and BDNF(±) groups at the same volume. At the third day of Tm or saline injection, the animals were sacrificed, and blood and liver samples were harvested. For histological and immunohistochemical analysis, a piece of liver was fixed in 10% neutral formalin. For ELISA measurements, ∼250–300 mg liver tissue was homogenised in ice-cold PBS (10 mg/ml). The supernatants obtained from centrifugation (at 5000 × g for 5 min) of tissue homogenates were stored at −80 °C until tested by ELISA. Serum samples were also stored at −80 °C for BDNF measurements.