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21.
Vincenza Dolo Sandra D'Ascenzo Maurizio Sorice Antonio Pavan Mariateresa Sciannamblo Alessandro Prinetti Vanna Chigorno Guido Tettamanti Sandro Sonnino 《Glycoconjugate journal》2000,17(3-4):261-268
This paper is the first report on the use of the electron microscopy autoradiography technique to detect metabolically tritium labeled sphingolipids in intact cells in culture.To label cell sphingolipids, human fibroblasts in culture were fed by a 24 hours pulse, repeated 5 times, of 3×10–7 M [1-3H]sphingosine. [1-3H]sphingosine was efficently taken up by the cells and very rapidly used for the biosynthesis of complex sphingolipids, including neutral glycolipids, gangliosides, ceramide and sphingomyelin. The treatment with [1-3H]sphingosine did not induce any morphological alteration of cell structures, and well preserved cells, plasma membranes, and intracellular organelles could be observed by microscopy.Ultrathin sections from metabolic radiolabeled cells were coated with autoradiographic emulsion. One to four weeks of exposition resulted in pictures where the location of radioactive sphingolipids was evidenced by the characteristic appearance of silver grains as irregular coiled ribbons of metallic silver. Radioactive sphingolipids were found at the level of the plasma membranes, on the endoplasmic reticulum and inside of cytoplasmic vesicles. Thus, electron microscopy autoradiography is a very useful technique to study sphingolipid-enriched membrane domain organization and biosynthesis. 相似文献
22.
Ali Munaim Yousif Michele Minopoli Katia Bifulco Vincenzo Ingangi Gioconda Di Carluccio Francesco Merlino Maria Letizia Motti Paolo Grieco Maria Vincenza Carriero 《PloS one》2015,10(5)
The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88-92 is the minimal sequence required to induce cell motility. We and others have previously documented that the uPAR88-92 sequence, even in the form of synthetic linear peptide (SRSRY), interacts with the formyl peptide receptor type 1 (FPR1), henceforth inducing cell migration of several cell lines, including monocytes. FPR1 is mainly expressed by mammalian phagocytic leukocytes and plays a crucial role in chemotaxis. In this study, we present evidence that the cyclization of the SRSRY sequence generates a new potent and stable inhibitor of monocyte trafficking. In rat basophilic leukaemia RBL-2H3/ETFR cells expressing high levels of constitutively activated FPR1, the cyclic SRSRY peptide ([SRSRY]) blocks FPR1 mediated cell migration by interfering with both internalization and ligand-uptake of FPR1. Similarly to RBL-2H3/ETFR cells, [SRSRY] competes with fMLF for binding to FPR1 and prevents agonist-induced FPR1 internalization in human monocyte THP-1 cells. Unlike scramble [RSSYR], [SRSRY] inhibits fMLF-directed migration of monocytes in a dose-dependent manner, with IC50 value of 0.01 nM. PMA-differentiated THP-1 cell exposure to fMLF gradient causes a marked cytoskeletal re-organization with the formation of F-actin rich pseudopodia that are prevented by the addition of [SRSRY]. Furthermore, [SRSRY] prevents migration of human primary monocytes and trans-endothelial migration of monocytes. Our findings indicate that [SRSRY] is a new FPR1 inhibitor which may suggest the development of new drugs for treating pathological conditions sustained by increased motility of monocytes, such as chronic inflammatory diseases. 相似文献
23.
Elena Turola Salvatore Petta Ester Vanni Fabiola Milosa Luca Valenti Rosina Critelli Luca Miele Livia Maccio Vincenza Calvaruso Anna L. Fracanzani Marcello Bianchini Nazarena Raos Elisabetta Bugianesi Serena Mercorella Marisa Di Giovanni Antonio Craxì Silvia Fargion Antonio Grieco Calogero Cammà Franco Cotelli Erica Villa 《Disease models & mechanisms》2015,8(9):1037-1046
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Matteo Astone Marco Pizzi Margherita Peron Alice Domenichini Vincenza Guzzardo Sonja T?chterle Natascia Tiso Massimo Rugge Dirk Meyer Francesco Argenton Andrea Vettori 《PloS one》2015,10(12)
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas, characterized by complex karyotypes. The molecular bases of such malignancy are poorly understood and efficient targeted molecular therapies are currently lacking. Here we describe a novel zebrafish model of MPNSTs, represented by the transgenic mutant line Tg(-8.5nkx2.2a:GFP)
ia2. ia2 homozygous animals displayed embryonic lethality by 72 hpf, while the heterozygotes develop visible tumor masses with high frequency in adulthood. Histological and immunohistochemical examination revealed aggressive tumors with either mesenchymal or epithelial features. The former (54% of the cases) arose either in the abdominal cavity, or as intrathecal/intraspinal lesions and is composed of cytokeratin-negative spindle cells with fascicular/storiform growth pattern consistent with zebrafish MPNSTs. The second histotype was composed by polygonal or elongated cells, immunohistochemically positive for the pan-cytokeratin AE1/AE3. The overall histologic and immunohistochemical features were consistent with a malignant epithelial neoplasm of possible gastrointestinal/pancreatic origin. With an integrated approach, based on microsatellite (VNTR) and STS markers, we showed that ia2 insertion, in Tg(-8.5nkx2.2a:GFP)
ia2 embryos, is associated with a deletion of 15.2 Mb in the telomeric portion of chromosome 1. Interestingly, among ia2 deleted genes we identified the presence of the 40S ribosomal protein S6 gene that may be one of the possible drivers for the MPNSTs in ia2 mutants. Thanks to the peculiar features of zebrafish as animal model of human cancer (cellular and genomic similarity, transparency and prolificacy) and the GFP tag, the Tg(-8.5nkx2.2a:GFP)
ia2 line provides a manageable tool to study in vivo with high frequency MPNST biology and genetics, and to identify, in concert with the existing zebrafish MPNST models, conserved relevant mechanisms in zebrafish and human cancer development. 相似文献
27.
Parker MF Barten DM Bergstrom CP Bronson JJ Corsa JA Deshpande MS Felsenstein KM Guss VL Hansel SB Johnson G Keavy DJ Lau WY Mock J Prasad CV Polson CT Sloan CP Smith DW Wallace OB Wang HH Williams A Zheng M 《Bioorganic & medicinal chemistry letters》2007,17(16):4432-4436
A series of N-alkylbenzenesulfonamides were developed from a high throughput screening hit. Classic and parallel synthesis strategies were employed to produce compounds with good in vitro and in vivo gamma-secretase activity. 相似文献
28.
Giardina P Autore F Faraco V Festa G Palmieri G Piscitelli A Sannia G 《Applied microbiology and biotechnology》2007,75(6):1293-1300
The subfamily of POXA3 laccase isoenzymes produced by the fungus Pleurotus ostreatus has been characterized as an example of the complexity and heterogeneity of fungal isoenzyme patterns. Two isoenzymes, POXA3a
and POXA3b, were previously purified, exhibiting an unusual heterodimeric structure composed of a large (67 kDa) and a small
(18 or 16 kDa) subunit. A unique gene encodes the large subunit of both POXA3a and POXA3b, but alternative splicing produces
two variants—differing for an insertion of four amino acids—for each isoenzyme. Two genes encoding POXA3a and POXA3b small
subunits have been identified, and the corresponding amino acid sequences show only two amino acid substitutions. The 18-
and 16-kDa subunits of both POXA3a and POXA3b differ for N-glycosylation at Asn150 of the 16-kDa subunit. The POXA3 large subunit 3D model allows us to highlight peculiarities of this
molecule with respect to the laccases whose 3D structures are known. 相似文献
29.
Parker MF Bronson JJ Barten DM Corsa JA Du W Felsenstein KM Guss VL Izzarelli D Loo A McElhone KE Marcin LR Padmanabha R Pak R Polson CT Toyn JH Varma S Wang J Wong V Zheng M Roberts SB 《Bioorganic & medicinal chemistry letters》2007,17(21):5790-5795
A series of amino-caprolactam sulfonamides were developed from a screening hit. Compounds with good in vitro and in vivo gamma-secretase activity are reported. 相似文献
30.
Catania MV D'Antoni S Bonaccorso CM Aronica E Bear MF Nicoletti F 《Molecular neurobiology》2007,35(3):298-307
Group I metabotropic glutamate receptors (mGlu1 and mGlu5) are coupled to polyphosphoinositide hydrolysis and are involved
in activity-dependent forms of synaptic plasticity, both during development and in the adult life. Group I mGlu receptors
can also regulate proliferation, differentiation, and survival of neural stem/progenitor cells, which further support their
role in brain development. An exaggerated response to activation of mGlu5 receptors may underlie synaptic dysfunction in Fragile
X syndrome, the most common inherited form of mental retardation. In addition, group I mGlu receptors are overexpressed in
dysplastic neurons of focal cortical dysplasia and hemimegaloencephaly, which are disorders of cortical development associated
with chronic epilepsy. Drugs that block the activity of group I mGlu receptors (in particular, mGlu5 receptors) are potentially
helpful for the treatment of Fragile X syndrome and perhaps other neurodevelopmental disorders. 相似文献