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31.
Laura?Quotti Tubi Carmela?GurrieriEmail author Alessandra?Brancalion Laura?Bonaldi Roberta?Bertorelle Sabrina?Manni Laura?Pavan Federica?Lessi Renato?Zambello Livio?Trentin Fausto?Adami Maria?Ruzzene Lorenzo?A?Pinna Gianpietro?SemenzatoEmail author Francesco?Piazza 《Journal of hematology & oncology》2013,6(1):78
Background
The involvement of protein kinase CK2 in sustaining cancer cell survival could have implications also in the resistance to conventional and unconventional therapies. Moreover, CK2 role in blood tumors is rapidly emerging and this kinase has been recognized as a potential therapeutic target. Phase I clinical trials with the oral small ATP-competitive CK2 inhibitor CX-4945 are currently ongoing in solid tumors and multiple myeloma.Methods
We have analyzed the expression of CK2 in acute myeloid leukemia and its function in cell growth and in the response to the chemotherapeutic agent daunorubicin We employed acute myeloid leukemia cell lines and primary blasts from patients grouped according to the European LeukemiaNet risk classification. Cell survival, apoptosis and sensitivity to daunorubicin were assessed by different means. p53-dependent CK2-inhibition-induced apoptosis was investigated in p53 wild-type and mutant cells.Results
CK2α was found highly expressed in the majority of samples across the different acute myeloid leukemia prognostic subgroups as compared to normal CD34+ hematopoietic and bone marrow cells. Inhibition of CK2 with CX-4945, K27 or siRNAs caused a p53-dependent acute myeloid leukemia cell apoptosis. CK2 inhibition was associated with a synergistic increase of the cytotoxic effects of daunorubicin. Baseline and daunorubicin-induced STAT3 activation was hampered upon CK2 blockade.Conclusions
These results suggest that CK2 is over expressed across the different acute myeloid leukemia subsets and acts as an important regulator of acute myeloid leukemia cell survival. CK2 negative regulation of the protein levels of tumor suppressor p53 and activation of the STAT3 anti-apoptotic pathway might antagonize apoptosis and could be involved in acute myeloid leukemia cell resistance to daunorubicin.32.
33.
Manganese Phosphite in Coffee Defence against Hemileia vastatrix,the Coffee Rust Fungus: Biochemical and Molecular Analyses
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34.
Caio Loureiro Salgado Emmanoel Loss Dias Lorenzzo Lyrio Stringari Luciana Polaco Covre Reynaldo Dietze Fausto Edmundo Lima Pereira Herbet Leonel de Matos Guedes Bartira Rossi-Bergmann Daniel Claudio Oliveira Gomes 《Microbes and infection / Institut Pasteur》2019,21(7):328-335
The use of adjuvants in vaccine formulations is a well-established practice to improve immunogenicity and protective immunity against diseases. Previously, we have demonstrated the feasibility of intranasal vaccination with the antigen of killed Leishmania amazonensis promastigotes (LaAg) against experimental leishmaniasis. In this work, we sought to optimize the immunogenic effect and protective immunity against murine visceral leishmaniasis conferred by intranasal delivery of LaAg in combination with a synthetic TLR1/TLR2 agonist (Pam3CSK4). Intranasal vaccination with LaAg/PAM did not show toxicity or adverse effects, induced the increase of delayed-type hypersensitivity response and the production of inflammatory cytokines after parasite antigen recall. However, mice vaccinated with LaAg/PAM and challenged with Leishmania infantum presented significant reduction of parasite burden in both liver and spleen, similar to those vaccinated with LaAg. Although LaAg/PAM intranasal vaccination had induced higher frequencies of specific CD4+ and CD8+ T cells and increased levels of IgG2a antibody isotype in serum, both LaAg and LaAg/PAM groups presented similar levels of IL-4 and IFN-y and decreased production of IL-10 when compared to controls. Our results provide the first evidence of the feasibility of intranasal immunization with antigens of killed Leishmania in association with a TLR agonist, which may be explored for developing an effective and alternative strategy for vaccination against visceral leishmaniasis. 相似文献
35.
Chiara Salvesi Stefania Silvi Dennis Fiorini Serena Scortichini Gianni Sagratini Francesco A. Palermo Renato De Leone Nadaniela Egidi Lorella Fatone Carlo Cifani Amedeo Amedei Francesca Scocchera Mara Morici Beatrice Gatto Fausto Mannucci Valerio Valeriani Marco Malavasi Sara Servili Andrea Casula Andrea Cresci Ivano Corradetti Francesco Carpi Matteo Picciolini Maria Magdalena Coman Maria Cristina Verdenelli 《Journal of applied microbiology》2022,133(5):2941-2953
36.
The morphology and ultrastructure of the larval spiracle system of three phlebotomine sandfly species, Phlebotomus perniciosus, P. perfiliewi and P. papatasi, were examined by scanning (SEM) and transmission (TEM) electron microscopy and by confocal scanning laser microscopy (CSLM). During larval development, thoracic and abdominal spiracles show considerable modifications. In fourth instar larvae, the spiracles consist of a plate with a sclerotized central portion and a peripheral circle of papillae. The latter is distinctive in the larvae of P. papatasi, which are readily distinguished from the other species. Opening clefts across the papillae communicate with an internal chamber that encircles an electrondense plug. Many cylindrical projections cross the chamber, uniting the central plug with the larval body, forming an air filter. Spiracular development in successive larval instars has both a taxonomic and adaptive value. 相似文献
37.
Botta D Franklin CC White CC Krejsa CM Dabrowski MJ Pierce RH Fausto N Kavanagh TJ 《Free radical biology & medicine》2004,37(5):632-642
Glutathione (GSH) is important in free radical scavenging, maintaining cellular redox status, and regulating cell survival in response to a wide variety of toxicants. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), which is composed of catalytic (GCLC) and modifier (GCLM) subunits. To determine whether increased GSH biosynthetic capacity enhances cellular resistance to tumor necrosis factor-alpha- (TNF-alpha-) induced apoptotic cell death, we have established several mouse liver hepatoma (Hepa-1) cell lines overexpressing GCLC and/or GCLM. Cells overexpressing GCLC alone exhibit modest increases in GCL activity, while cells overexpressing both subunits have large increases in GCL activity. Importantly, cells overexpressing both GCL subunits exhibit increased resistance to TNF-induced apoptosis as judged by a loss of redox potential; mitochondrial membrane potential; translocation of cytochrome c to the cytoplasm; and activation of caspase-3, caspase-8, and caspase-9. Analysis of the effects of TNF on these parameters indicates that maintaining mitochondrial integrity mediates this protective effect in GCL-overexpressing cells. 相似文献
38.
In order to study the genetic structure of the Adriatic shared stock of red mullet (Mullus barbatus), we developed a set of dinucleotide microsatellite markers. A dinucleotide-enriched genomic library was obtained, and 6 polymorphic dinucleotide loci were successfully optimized. The markers showed high expected heterozygosity (from 0.68 to 0.92) and allele number (from 12 to 33); thus they appear to be suitable for detecting genetic differences in the population of red mullet. Four Adriatic samples were subsequently analyzed for microsatellite variation, and the results showed subtle but statistically significant genetic differentiation, indicating that the Adriatic red mullet may group into local, genetically isolated populations. No correlation between geographic distance and genetic differentiation was observed. In addition, the evidence of recent bottlenecks in the Adriatic samples indicates that the observed population subdivision might reflect random local allelic variations, generated by reproductive success, survival rates, or fishing pressure. 相似文献
39.
This paper presents the results of a MM2 study of the adsorption of oleic acid and ethanol/water in the tunnel and active-site models of lipases from Candida rugosa and Candida antarctica B. The role of an interface polar/no polar in the opening of C. rugosa lipase's lid is also addressed, discussed and analyzed at the level of the conformational changes needed to achieve the lipase open form. The adsorption of oleic acid and alcohols considering C. antarctica B, a lipase not interfacially activated, is also presented. In this case, the tunnel is shorter than in case of C. rugosa lipase. Two different pockets can be visualized at the active site-tunnel model of C. antarctica B lipase: one for the acyl group and another for the alcohol. Wrong location of alcohol and oleic acid severely hinders reaction because it hinders the H-transfer to histidine, a key step in the reaction mechanism. Right location of alcohol decreases the possibility of alcohol inhibition. In the case of C. rugosa, no restrictions for ethanol/water location are found. For that lipase, a second adsorption site for oleic acid (outside the tunnel) is presented. This site is the exit tunnel of the ester product when oleic acid is adsorbed in the tunnel. Experimental results of our own that correlate with this study are presented. 相似文献
40.
A phaseolin domain involved directly in trimer assembly is a determinant for binding by the chaperone BiP
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Foresti O Frigerio L Holkeri H de Virgilio M Vavassori S Vitale A 《The Plant cell》2003,15(10):2464-2475
The binding protein (BiP; a member of the heat-shock 70 family) is a major chaperone of the endoplasmic reticulum (ER). Interactions with BiP are believed to inhibit unproductive aggregation of newly synthesized secretory proteins during folding and assembly. In vitro, BiP has a preference for peptide sequences enriched in hydrophobic amino acids, which are expected to be exposed only in folding and assembly intermediates or in defective proteins. However, direct information regarding sequences recognized in vivo by BiP on real proteins is very limited. We have shown previously that newly synthesized monomers of the homotrimeric storage protein phaseolin associate with BiP and that phaseolin trimerization in the ER abolishes such interactions. Using different phaseolin constructs and green fluorescent protein (GFP) fusion proteins, we show here that one of the two alpha-helical regions of polypeptide contact in phaseolin trimers (35 amino acids located close to the C terminus and containing three potential BiP binding sites) effectively promotes BiP association with phaseolin and with secretory GFP fusions expressed in transgenic tobacco or in transfected protoplasts. We also show that overexpressed BiP transiently sequesters phaseolin polypeptides. We conclude that one of the regions of monomer contact is a BiP binding determinant and suggest that during the synthesis of phaseolin, the association with BiP and trimer formation are competing events. Finally, we show that the other, internal region of contact between monomers is necessary for phaseolin assembly in vivo and contains one potential BiP binding site. 相似文献