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G De Falco

Publications and source records attributed to G De Falco.

24 records · Page 2Linked to original sources
PubMed1997

Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase.

IL-6 is a multifunctional cytokine involved in hemopoiesis, immune regulation, inflammation, neural development, and infection. IL-6 belongs to a family of related cytokines that includes leukemia inhibitory factor, oncostatin M, IL-11, ciliary neurotropic factor, and cardiotropin-1, all of which initiate signaling through a receptor-associated gp130. IL-6 induces homodimerization of gp130 and activates the Jak/STAT pathway of signal transduction. In addition, IL-6 stimulates the mitogen-activated protein kinases designated ERK (extracellular signal-regulated kinase)-1 and -2. Activation of ERK-1 and -2 may involve the Src homology-2 containing proteins Shc and Grb2. Here we provide evidence that Shc could function as signaling molecules for IL-6 in DeFew-IL-6R/gp130 cells, a human B lymphoma cell line engineered to express high levels of both the IL-6R (p80) and the gp130 subunit. IL-6 was shown to promote the rapid tyrosine phosphorylation of gp130, Jak2, and Shc proteins. Moreover, Shc associated both in vivo and in vitro with phosphorylated gp130 through the Shc-Src homology-2 domain. We also report that Shc bound to activated Jak2 by using the Shc amino terminal phosphotyrosine interaction domain. Following IL-6 stimulation, Shc physically associated with Grb2. Thus, the data point to Shc proteins as a functional link between the Jak2 and Ras pathways of IL-6 signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Regulation of HIV-1 long terminal repeats by interaction of C/EBP(NF-IL6) and NF-kappaB/Rel transcription factors.

We report the characterization of a CAAT enhancer-binding protein (C/EBP) (NF-IL6) element encompassing the region from -174 to -166 of the U3 long terminal repeat (LTR) region of HIV-1. This C/EBP cis sequence was found to bind to C/EBPbeta and C/EBPdelta factors in DNA band shift assay. Transfection of NTera-2 cells with a HIV-1-LTR CAT construct (pC15CAT), together with C/EBPbeta or C/EBPdelta expression plasmids showed that C/EBP proteins strongly activated the HIV-1 promoter. Deletions encompassing the C/EBP-binding site resulted in the enhancement of the LTR activation mediated by C/EBP proteins, suggesting that other sequences located 3' to -170 were indeed the target for C/EBP factors. This possibility was confirmed by using the pCD54E9CAT plasmid, in which the NF-kappaB enhancer was inserted 5' to the HIV-1 LTR TATA box. A NF-kappaB1(p50) expression plasmid was also utilized to test for functional co-operation between NF-kappaB and C/EBP factors. We observed that p50 middle dotC/EBPbeta and p50 middle dotC/EBPdelta complexes were generated in tested cells and strongly activated the HIV-1 LTR by binding to the NF-kappaB sequences. The physical association of NF-kappaB1(p50) with C/EBP factors was assayed by direct interaction of in vitro translated p50 proteins with C/EBPbeta or C/EBPdelta produced as glutathione S-transferase fusion proteins. Moreover, p50 middle dotC/EBPbeta complexes were observed in vivo by using DNA affinity studies with biotinylated NF-kappaB oligonucleotides. By using mutant forms of p50 or C/EBPbeta proteins we found that the transactivation of HIV-1 LTR by p50 middle dotC/EBPbeta complexes required the DNA-binding domain of p50 and the transcription activation domain of C/EBPbeta.

Binding Sites↗
PubMedDate not supplied

Vasoactive intestinal peptide stimulation modulates the expression of Bcl-2 family members in the adrenal gland of the lizard Podarcis sicula.

The adrenal gland of the lizard Podarcis sicula is formed by a dorsal ribbon of chromaffin cells, generally defined as medullary tissue, arranged along a central part of steroidogenic cells considered as cortical tissue. These two tissues produce catecholamines and steroids as part of the hypothalamo-hypophyseal-adrenal gland axis. Recent studies have demonstrated that Podarcis sicula adrenal gland is not only under hypothalamo-hypophyseal axis control but that several peptides may influence the physiological activity of the gland; among these, vasoactive intestinal peptide is able to enhance strongly both catecholamine and steroid hormone production. The aim of the present study was to verify whether vasoactive intestinal peptide administration could become deleterious. For this reason, we monitored the pattern of expression of two members of the Bcl-2 family, Bcl-2 and Bax, in control and vasoactive intestinal peptide treated specimens. Furthermore, we also tested if peptide treatment induces apoptosis by TUNEL assay.

Adrenal Glands↗
PubMedDate not supplied

Organic pollution in a Ramsar site (Piallassa Baiona, northern Adriatic Sea).

A core collected in the Piallassa Baiona lagoon, a salt-marsh area already studied for Hg contamination related to nearby industrial sites, was analysed for organic micropollutants. Surface sediments show high concentrations of total PCBs (1148 ng g-1), PCDD/Fs (64 ng g-1) and PAHs (4801 ng g-1). According to a sedimentation rate of 0.4 cm y-1, the high increases in total PAH, PCB and PCDD/F concentrations began in the 1960s and peaked in the 1970s, in parallel with the highest Hg concentrations. Instead, the recent contamination, which primarily involves PCBs and PCDD/Fs, has been observed to be unrelated to Hg concentrations. Organic micropollutant concentrations in the sample core were compared with the sediment quality criteria provided by international guidelines, and revealed high toxic potential. This heavy contamination was also confirmed by comparison with similar environments, particularly the Lagoon of Venice. Further investigations are needed to understand better the sources of the recent contamination and to explain the different transfer pathways involved during sedimentation of the "old" material, dumped 20-30 years ago.

Environmental Monitoring↗
PubMedDate not supplied

Angiogenesis, angiogenic factor expression and hematological malignancies.

Solid tumor growth consists of an avascular and a subsequent vascular phase. Several studies have now shown that, as in solid tumors, angiogenesis also plays a critical role in the progression of hematological malignancies. Monoclonal gammopathy of undetermined significance (MGUS) and non-active to active multiple myeloma (MM) progress when plasma cells induce angiogenesis and this in turn promotes progression. The increased bone marrow neovascularization, increased angiogenic and proteolytic potential of plasma cells may explain the frequent occurrence of extramedullary localization in MM. As observed in active MM, enhanced bone marrow neovascularization is apparent in acute untreated lymphoblastic leukemia. In B-cell non-Hodgkin's lymphomas, angiogenesis is significantly enhanced in relation to progression. Angiostatic molecules, such as thalidomide, could also be considered for the clinical management of hematological tumors.

Angiogenesis Inducing Agents↗