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Irene Zornetta Lucia Brandi Blythe Janowiak Federica Dal Molin Fiorella Tonello R. John Collier Cesare Montecucco 《Cellular microbiology》2010,12(10):1435-1445
To investigate the cell entry and intracellular trafficking of anthrax oedema factor (EF) and lethal factor (LF), they were C‐terminally fused to the enhanced green fluorescent protein (EGFP) and monomeric Cherry (mCherry) fluorescent proteins. Both chimeras bound to the surface of BHK cells treated with protective antigen (PA) in a patchy mode. Binding was followed by rapid internalization, and the two anthrax factors were found to traffic along the same endocytic route and with identical kinetics, indicating that their intracellular path is essentially dictated by PA. Colocalization studies indicated that anthrax toxins enter caveolin‐1 containing compartments and then endosomes marked by phoshatidylinositol 3‐phoshate and Rab5, but not by early endosome antigen 1 and transferrin. After 40 min, both EF and LF chimeras were observed to localize within late compartments. Eventually, LF and EF appeared in the cytosol with a time‐course consistent with translocation from late endosomes. Only the EGFP derivatives reached the cytosol because they are translocated by the PA channel, while the mCherry derivatives are not. This difference is attributed to a higher resistance of mCherry to unfolding. After translocation, LF disperses in the cytosol, while EF localizes on the cytosolic face of late endosomes. 相似文献
63.
Francesco Di Girolamo Jhessica Alessandroni Paolo Somma Fiorella Guadagni 《Journal of Proteomics》2010,73(3):667-677
Biological specimen collection and storage are an integral component of serum proteomics research. Although many efforts have been posed to address the effects of pre-analytical procedures, standardized protocols for collection and storage of samples for Low Molecular Weight (LMW) proteome profiling are still needed.Here we report a systematic analysis on the influence of pre-analytical factors [clotting times, temperature and time storage, addition of protease inhibitor (PI)] on serum LMW proteome profiling. Moreover, a comparison between manual versus automated peptide purification by functionalized magnetic bead-based MALDI-MS approach was performed. The results demonstrated best serum LMW proteins recovery and stability using a clotting time between 1 and 2 h, with serum stored up to 2 h either at room temperature or at 4 °C, independently of PI addition. PI addition to whole blood resulted in a lower number of LMW peaks detected. Finally, minimal effects on serum proteome profiles were observed after 1-month storage at ? 80 °C, independently of PI addition on whole blood and/or serum.In conclusion, the use of standardized pre-analytical and storage procedures together with an automated peptide purification might minimize potential bias on serum LMW profiling results, thus allowing a better homogeneity and reproducibility in future proteomics studies. 相似文献
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Sabrina Boscolo Andrea Lorenzon Daniele Sblattero Fiorella Florian Marco Stebel Roberto Marzari Tarcisio Not Daniel Aeschlimann Alessandro Ventura Marios Hadjivassiliou Enrico Tongiorgi 《PloS one》2010,5(3)
Background
Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one.Methods
We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice.Conclusion
The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia. 相似文献66.
Bianchi M Rizza T Verrigni D Martinelli D Tozzi G Torraco A Piemonte F Dionisi-Vici C Nobili V Francalanci P Boldrini R Callea F Santorelli FM Bertini E Carrozzo R 《Biochemical and biophysical research communications》2011,415(2):300-304
Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies. 相似文献
67.
In Saccharomyces cerevisiae the Cdc25/Ras/cAMP pathway is involved in cell growth and proliferation regulation. Ras proteins are regulated by Ira1/2 GTPase activating proteins (GAPs) and Cdc25/Sdc25 guanine nucleotide exchange factors (GEFs).Most of cytosolic Cdc25 protein was found on internal membranes in exponentially growing cells, while upon incubation in a buffer with no nutrients it is re-localized to plasma membrane. The overexpression of Tpk1 PKA catalytic subunit also induces Cdc25 export from the nucleus, involving two serine residues near the Nuclear Localization Site (NLS): mutation of Ser825 and Ser826 to glutamate is sufficient to exclude physiologically expressed Cdc25 from the nucleus, mimicking Tpk1 overproduction effect. Mutation of these Ser residues to Ala abolishes the effect of nuclear export induced by Tpk1 overexpression on a Cdc25eGFP fusion. Moreover, mutation of these residues affects PKA-related phenotypes such as heat shock resistance, glycogen content and cell volume. 相似文献
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Francesca Orso Fiorella Balzac Marco Marino Antonio Lembo Saverio Francesco Retta Daniela Taverna 《Biochemical and biophysical research communications》2013
miR-21 is overexpressed in tumors and it displays oncogenic activity. Here, we show that expression of miR-21 in primary tumors anticorrelates with KRIT1/CCM1, an interacting partner of the Ras-like GTPase Rap1, involved in Cerebral Cavernous Malformations (CCM). We present evidences that miR-21 silences KRIT1 by targeting its mRNA 3′UTR and that this interaction is involved in tumor growth control. In fact, miR-21 over-expression or KRIT1 knock-down promote anchorage independent tumor cell growth compared to controls, whereas the opposite is observed when anti-miR-21 or KRIT1 overexpression are employed. Our findings suggest that miR-21 promotes tumor cell growth, at least in part, by down-modulating the potential tumor suppressor KRIT1. 相似文献
70.
Ulivi V Giannoni P Gentili C Cancedda R Descalzi F 《Journal of cellular biochemistry》2008,104(4):1393-1406
Studying cartilage differentiation, we observed the emergence of inflammation-related proteins suggesting that a common pathway was activated in cartilage differentiation and inflammation. In the present paper, we investigated the expression pathway of the inflammation-related enzyme Cyclooxygenase-2 (COX-2) during differentiation and inflammatory response of the chondrocytic cell line MC615. Cells were cultured either as (i) proliferating prechondrogenic cells expressing type I collagen or (ii) differentiated hyperconfluent cells expressing Sox9 and type II collagen. The p38 and the NF-kB pathways were investigated in standard conditions and after inflammatory agents treatment. NF-kB was constitutively activated in differentiated cells. The activation level of NF-kB in differentiated cells was comparable to the level in proliferating cells treated with the inflammatory agent LPS. In both cases, p65 was bound to the NF-kB consensus sequence of COX-2 promoter. p38, constitutively activated in differentiated cells, was activated in proliferating cells by treatment with LPS or IL-1alpha. In stimulated proliferating cells the two pathways are connected since addition of the p38-specific inhibitor SB203580 inhibited p38 activation, significantly reduced NF-kB activation and repressed COX-2 synthesis indicating that p38 is upstream NF-kB activation and COX-2 synthesis. In differentiated cells, the treatment with the inflammatory agent neither enhance NF-kB activation, nor synthesis of COX-2 while the addition of SB203580 neither repressed activation of p38, nor COX-2 synthesis, suggesting a constitutive activation of a p38/NF-kB/COX2 pathway. Our data indicate that in chondrocytes, COX-2 is expressed via p38 activation/NF-kB recruitment during both differentiation and inflammatory response. 相似文献