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51.
Pucci B De Felice M Rocco M Esposito F De Falco M Esposito L Rossi M Pisani FM 《The Journal of biological chemistry》2007,282(17):12574-12582
Mini-chromosome maintenance (MCM) proteins form ring-like hexameric complexes that are commonly believed to act as the replicative DNA helicase at the eukaryotic/archaeal DNA replication fork. Because of their simplified composition with respect to the eukaryotic counterparts, the archaeal MCM complexes represent a good model system to use in analyzing the structural/functional relationships of these important replication factors. In this study the domain organization of the MCM-like protein from Sulfolobus solfataricus (Sso MCM) has been dissected by trypsin partial proteolysis. Three truncated derivatives of Sso MCM corresponding to protease-resistant domains were produced as soluble recombinant proteins and purified: the N-terminal domain (N-ter, residues 1-268); a fragment comprising the AAA+ and C-terminal domains (AAA+-C-ter, residues 269-686); and the C-terminal domain (C-ter, residues 504-686). All of the purified recombinant proteins behaved as monomers in solution as determined by analytical gel filtration chromatography, suggesting that the polypeptide chain integrity is required for stable oligomerization of Sso MCM. However, the AAA+-C-ter derivative, which includes the AAA+ motor domain and retains ATPase activity, was able to form dimers in solution when ATP was present, as analyzed by size exclusion chromatography and glycerol gradient sedimentation analyses. Interestingly, the AAA+-C-ter protein could displace oligonucleotides annealed to M13 single-stranded DNA although with a reduced efficiency in comparison with the full-sized Sso MCM. The implications of these findings for understanding the DNA helicase mechanism of the MCM complex are discussed. 相似文献
52.
Cannizzaro A Verga Falzacappa CV Martinelli M Misiti S Brunetti E Bucci B 《Journal of cellular physiology》2007,213(1):115-125
In search for innovative therapeutic agents for children neuroblastoma, the oxygen therapy could be considered an alternative anti-tumoral treatment. Given the physiochemical properties of O(2/3) gas mixture including fairly low aqueous solubility and spreading, and the interesting perspective of hyperoxia, we analyzed the inhibitory effect of O(2/3) treatment on two human neuroblastoma cell lines (SK-N-SH and SK-N-DZ). In this study, we demonstrated that O(2/3) treatment was able to induce cell growth inhibition and cell cycle perturbation in both cell lines. We observed an arrest at G(2) phase, accompanied by an alteration in the expression and localization of cyclin B1/cdk1 complex and a reduction in its activity in SK-N-SH cells. This reduction was consistent with the increase in both Wee1 and chk1 protein levels. On the contrary, O(2/3) induced apoptosis in SK-N-DZ cells via caspase 3 activation and Poly ADP-ribose polymerase-1 (PARP) cleavage, associated with an increase in the pro-apoptotic Bax protein. Consequently, we considered the possibility of improving the responsiveness to chemotherapeutic agents such as Cisplatin, Etoposide, and Gemcitabine in combination with O(2/3) treatment. The combined treatments produced a stronger cell inhibitory effect than Cisplatin and Etoposide used alone in SK-N-SH cells. On the contrary, the combination data were not significantly different from O(2/3) treatment alone in SK-N-DZ cells, thus suggesting that the obtained changes in cell growth inhibition were due to the effect of O(2/3) alone. 相似文献
53.
Bucci G González-Martínez SC Le Provost G Plomion C Ribeiro MM Sebastiani F Alía R Vendramin GG 《Molecular ecology》2007,16(10):2137-2153
Some 1339 trees from 48 Pinus pinaster stands were characterized by five chloroplast microsatellites, detecting a total of 103 distinct haplotypes. Frequencies for the 16 most abundant haplotypes (p(k) > 0.01) were spatially interpolated over a lattice made by 430 grid points. Fitting of spatially interpolated values on raw haplotype frequencies at the same geographical location was tested by regression analysis. A range-wide 'diversity map' based on interpolated haplotype frequencies allowed the identification of one 'hotspot' of diversity in central and southeastern Spain, and two areas of low haplotypic diversity located in the western Iberian peninsula and Morocco. Principal component analysis (PCA) carried out on haplotypes frequency surfaces allowed the construction of a colour-based 'synthetic' map of the first three PC components, enabling the detection of the main range-scale genetic trends and the identification of three main 'gene pools' for the species: (i) a 'southeastern' gene pool, including southeastern France, Italy, Corsica, Sardinia, Pantelleria and northern Africa; (ii) an 'Atlantic' gene pool, including all the western areas of the Iberian peninsula; and (iii) a 'central' gene pool, located in southeastern Spain. Multivariate and AMOVA analyses carried out on interpolated grid point frequency values revealed the existence of eight major clusters ('gene zones'), whose genetic relationships were related with the history of the species. In addition, demographic models showed more ancient expansions in the eastern and southern ranges of maritime pine probably associated to early postglacial recolonization. The delineation of the gene zones provides a baseline for designing conservation areas in this key Mediterranean pine. 相似文献
54.
Bontempo P Mita L Miceli M Doto A Nebbioso A De Bellis F Conte M Minichiello A Manzo F Carafa V Basile A Rigano D Sorbo S Castaldo Cobianchi R Schiavone EM Ferrara F De Simone M Vietri M Cioffi M Sica V Bresciani F de Lera AR Altucci L Molinari AM 《The international journal of biochemistry & cell biology》2007,39(10):1902-1914
Curative properties of some medicinal plants such as the Feijoa sellowiana Bert. (Myrtaceae), have been often claimed, although the corresponding molecular mechanism(s) remain elusive. We report here that the Feijoa acetonic extract exerts anti-cancer activities on solid and hematological cancer cells. Feijoa extract did not show toxic effects on normal myeloid progenitors thus displaying a tumor-selective activity. In the Feijoa acetonic extract, fractionation and subsequent purification and analyses identified Flavone as the active component. Flavone induces apoptosis which is accompanied by caspase activation and p16, p21 and TRAIL over-expression in human myeloid leukemia cells. Use of ex vivo myeloid leukemia patients blasts confirms that both the full acetonic Feijoa extract and its derived Flavone are able to induce apoptosis. In both cell lines and myeloid leukemia patients blasts the apoptotic activity of Feijoa extract and Flavone is accompanied by increase of histone and non-histone acetylation levels and by HDAC inhibition. Our findings show for the first time that the Feijoa apoptotic active principle is the Flavone and that this activity correlates with the induction of HDAC inhibition, supporting the hypothesis of its epigenetic pro-apoptotic regulation in cancer systems. 相似文献
55.
D'Alessio A Cerchia L Amelio I Incoronato M Condorelli G de Franciscis V 《Cellular signalling》2007,19(6):1193-1200
The balance between specific signals from different growth factors dictates the biological response of mammalian cells including cell proliferation, differentiation and survival. PC12 cells represent a model of choice to compare the signalling of differentiative growth factors, as NGF, and of mitogenic growth factors, as EGF. In these cells the prolonged activity of the ERK kinase dictates the decision of cells to differentiate. Here we focused on the cytosolic tyrosine phosphatase Shp2 as an established regulator of the Ras-ERK cascade, to elucidate its involvement in determining the stimulation-dependent PC12 cell fate. To this end, we generated PC12 derived cell lines that express the interfering mutant of Shp2 under a tetracycline-inducible promoter. Our findings show that Shp2 participates to the opposite effects induced in PC12 cells by EGF and NGF and that the interactions with the multidocking Gab2 protein mediate such effects. 相似文献
56.
Marracci S Casola C Bucci S Ragghianti M Ogielska M Mancino G 《Development genes and evolution》2007,217(5):395-402
57.
Musumeci D Roviello GN Moccia M Pedone C Bucci EM Sapio R Valente M Fumero S 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1447-1450
In this work we explore the ability of a chimeric LNA/DNA bent duplex, in which the kink is induced by 2 unpaired adenines in the middle of one strand, to bind HMGB1, a protein involved in many inflammatory processes. The LNA/DNA duplex was compared with the corresponding full DNA and PNA/DNA chimera duplexes from a thermodynamic and spectroscopic point of view. 相似文献
58.
Mariarosaria Galeano Francesca Polito Alessandra Bitto Natasha IrreraGiuseppe M. Campo Angela AvenosoMargherita Calò Patrizia Lo CascioLetteria Minutoli Mauro BaroneFrancesco Squadrito Domenica Altavilla 《生物化学与生物物理学报:疾病的分子基础》2011,1812(7):752-759
Hyaluronic acid (HA), an essential component of the extracellular matrix, is an efficient space filler that maintains hydration, serves as a substrate for assembly of proteoglycans and is involved in wound healing. Although numerous pieces of evidence demonstrate beneficial effects in promoting wound healing in diabetes, a systemic approach has never been tested. We used an incisional wound healing model in genetically diabetic mice to test the effects of systemic injection of HA. Diabetic (n = 56) and normoglycemic (n = 56) mice were subjected to incision and randomized (8 groups of 7 animals each) to receive HA at different doses, 7.5, 15 and 30 mg/kg/i.p., or vehicle (0.9% NaCl solution) for 12 days. At the end of the experiment animals were sacrificed and skin wounds were excised for histological, biochemical and molecular analysis. Histology revealed that the most effective dose to improve wound repair and angiogenesis in diabetic mice was 30 mg/kg. Furthermore HA injection (30 mg/kg) improved the altered healing pattern in diabetic animals, increased skin remodeling proteins TGF-β and transglutaminase-II and restored the altered expression of cyclin B1/Cdc2 complex. Evaluation of skin from diabetic animals injected with HA revealed also an increase in HA content, suggesting that systemic injection may be able to restore the reduced intracellular HA pool of diabetic mice. Finally HA markedly improved skin mechanical properties. These promising results, if confirmed in a clinical setting, may improve the care and management of diabetic patients. 相似文献
59.
This work concerns a dithymine tetrapeptide, which can be seen as a new analogue of a dinucleoside monophosphate, made of both unfunctionalized and thymine-containing L-serine units alternated in the sequence. The new nucleopeptide was obtained on the solid phase by two different synthetic strategies. The first one is suitable to easily realize nucleopeptides with homonucleobase sequences, obtained by assembling an oligoserine backbone and then simultaneously coupling the free serine hydroxyl groups with the carboxymethylated nucleobase. The other strategy, which makes use of a Fmoc-protected nucleo-L-serine monomer, allows for the obtainment of nucleopeptides with mixed nucleobase sequences. CD spectroscopic studies and laser light scattering experiments, performed on solutions of the novel nucleopeptide, suggested the formation of supramolecular networks based on the self-assembly of the dithymine tetrapeptide molecules. Furthermore, CD binding studies with natural nucleic acids revealed a very weak interaction between the nucleopeptide and DNA (but not RNA). Molecular networks based on this biodegradable and water-soluble nucleopeptide, which is more resistant in plasma than standard tetrapeptides (and oligopeptides), contain a hydrophobic core which could provide the necessary environment to incorporate poorly water-soluble drugs, as evidenced by fluorescence spectroscopy. Furthermore, our studies evidenced that the structure of the tetrapeptide-based supramolecular assembly can be modified by metal ions as evidenced by UV interaction studies with Cu(2+). 相似文献
60.
Laatikainen LE Incoronato M Castellone MD Laurila JP Santoro M Laukkanen MO 《PloS one》2011,6(8):e24456