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991.
In this work, we have devised an intracellular immunization strategy for the expression in high amounts of ATF-saporin, a targeted chimeric toxin constituted by the ATF receptor binding domain of human urokinase and the plant ribosome-inactivating protein saporin, which has been shown to be highly cytotoxic to target cells. This strategy may allow the production of highly toxic secretory proteins in eukaryotic cells, avoiding cell suicide caused by autointoxication. The procedure consists of equipping host cells with cytosolic neutralizing antibodies directed toward the toxic domain of the heterologous polypeptide. We show that this intracellular immunization is essential for the synthesis of correctly folded, biologically active ATF-SAP in the high amounts needed to investigate its in vivo anti-metastatic potential. Such a strategy should be generally useful for the production of toxic molecules of therapeutic value whose folding and maturation require transit through the eukaryotic secretory pathway. Fabbrini, M. S., Carpani, D., Soria, M. R., Ceriotti, A. Cytosolic immunization allows the expression of preATF-saporin chimeric toxin in eukaryotic cells. 相似文献
992.
993.
The synthesis of many of the proteins that are translocated into the
endoplasmic reticulum is accompanied by the co-translational attachment of
preformed oligosaccharide chains to certain Asn residues. These
glycoproteins can play a variety of roles in the mature proteins, including
the one of stabilizing the protein and protecting the polypeptide backbone
from the action of proteases. In addition, they can have a crucial function
during the process of polypeptide folding, when aggregation with other
proteins would hamper the acquisition of the native conformation. Their
influence on protein folding can be direct, or mediated by interactions
with endoplasmic reticulum-located molecular chaperones. The elucidation of
the mechanisms that govern glycoprotein folding in the plant endoplasmic
reticulum should contribute to the understanding of how much plant cells
rely on glycan chains to achieve the efficient folding of many proteins
under diverse environmental conditions. In addition, a better knowledge of
the level of conservation of the in vivo folding
mechanisms will be important for the exploitation of plant cells in the
production of heterologous glycoproteins.Keywords:
Calnexin, calreticulin, endoplasmic reticulum, glucose trimming,
glycoprotein stability.
相似文献
994.
Rosana Ferrari Silvana Maria Picolli Pugini Aldo Ivan Cespedes Arce Ernane Jose Xavier Costa Mariza Pires de Melo 《Cell biochemistry and function》2014,32(6):496-501
Tryptophan is an essential amino acid precursor of neurotransmitter serotonin and triptamine. During its metabolism, indole‐3‐acetic acid (IAA) is generated; this substance presents both antioxidant and prooxidant effects in different biological systems in addition to hipoglicemic effects. To date, electroencephalography (EEG) has been used to evaluate the temporal effect of several substances in neurotransmission. The goal of this study was to characterize the effect of IAA in the brain by analysing the EEG signal and evaluate the oxidative status by means of biochemical parameters. The EEG was acquired by using a noninvasive method, and the brain electric signal was analysed by advanced digital signal processing techniques to determinate the energy signal filtered in different band frequencies. Furthermore, the oxidative status of the brain was investigated by measuring the activity of antioxidant enzymes and lipid peroxidation as well as blood glucose rates of the animals treated with different doses of IAA. Our results showed the relationship of IAA administration with changes in EEG signals. The oxidative status of the brain was modified by IAA after 14 days of treatment. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
995.
Veronica Esposito Luigi Martino Giuseppe Citarella Antonella Virgilio Luciano Mayol Concetta Giancola Aldo Galeone 《Nucleic acids research》2010,38(6):2069-2080
Abasic sites represent the most frequent lesion in DNA. Since several events generating abasic sites concern guanines, this damage is particularly important in quadruplex forming G-rich sequences, many of which are believed to be involved in several biological roles. However, the effects of abasic sites in sequences forming quadruplexes have been poorly studied. Here, we investigated the effects of abasic site mimics on structural, thermodynamic and kinetic properties of parallel quadruplexes. Investigation concerned five oligodeoxynucleotides based on the sequence d(TGGGGGT), in which all guanines have been replaced, one at a time, by an abasic site mimic (dS). All sequences preserve their ability to form quadruplexes; however, both spectroscopic and kinetic experiments point to sequence-dependent different effects on the structural flexibility and stability. Sequences d(TSGGGGT) and d(TGGGGST) form quite stable quadruplexes; however, for the other sequences, the introduction of the dS in proximity of the 3′-end decreases the stability more considerably than the 5′-end. Noteworthy, sequence d(TGSGGGT) forms a quadruplex where dS does not hamper the stacking between the G-tetrads adjacent to it. These results strongly argue for the central role of apurinic/apyrimidinic site damages and they encourage the production of further studies to better delineate the consequences of their presence in the biological relevant regions of the genome. 相似文献
996.
997.
998.
Serrazanetti DI Ndagijimana M Sado-Kamdem SL Corsetti A Vogel RF Ehrmann M Guerzoni ME 《Applied and environmental microbiology》2011,77(8):2656-2666
Lactobacillus sanfranciscensis LSCE1 was selected as a target organism originating from recurrently refreshed sourdough to study the metabolic rerouting associated with the acid stress exposure during sourdough fermentation. In particular, the acid stress induced a metabolic shift toward overproduction of 3-methylbutanoic and 2-methylbutanoic acids accompanied by reduced sugar consumption and primary carbohydrate metabolite production. The fate of labeled leucine, the role of different nutrients and precursors, and the expression of the genes involved in branched-chain amino acid (BCAA) catabolism were evaluated at pH 3.6 and 5.8. The novel application of the program XCMS to the solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) data allowed accurate separation and quantification of 2-methylbutanoic and 3-methylbutanoic acids, generally reported as a cumulative datum. The metabolites coming from BCAA catabolism increased up to seven times under acid stress. The gene expression analysis confirmed that some genes associated with BCAA catabolism were overexpressed under acid conditions. The experiment with labeled leucine showed that 2-methylbutanoic acid originated also from leucine. While the overproduction of 3-methylbutanoic acid under acid stress can be attributed to the need to maintain redox balance, the rationale for the production of 2-methylbutanoic acid from leucine can be found in a newly proposed biosynthesis pathway leading to 2-methylbutanoic acid and 3 mol of ATP per mol of leucine. Leucine catabolism to 3-methylbutanoic and 2-methylbutanoic acids suggests that the switch from sugar to amino acid catabolism supports growth in L. sanfranciscensis in restricted environments such as sourdough characterized by acid stress and recurrent carbon starvation. 相似文献
999.
1000.
Ghimenti S Lomonaco T Onor M Murgia L Paolicchi A Fuoco R Ruocco L Pellegrini G Trivella MG Di Francesco F 《PloS one》2011,6(12):e28182