Search results for "Shock"
showing 10 items of 1248 documents
HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma
2015
We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10(4) cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and pr…
Heat shock proteins in fibrosis and wound healing: Good or evil?
2014
Heat shock proteins (HSPs) are key regulators of cell homeostasis, and their cytoprotective role has been largely investigated in the last few decades. However, an increasing amount of evidence highlights their deleterious effects on several human pathologies, including cancer, in which they promote tumor cell survival, proliferation and drug resistance. Therefore, HSPs have recently been suggested as therapeutic targets for improving human disease outcomes. Fibrotic diseases and cancer share several properties; both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interactions and communication and tissue invasion. The discovery of new HSP…
Abstract LB-085: A new role for LKB1 to regulate Heat Shock Protein 90 activity
2018
Abstract Approximately 30% of human non-small cell lung cancer (NSCLC) patients harbor a somatic KRAS mutation resulting, in aberrant activation of downstream signaling pathways that control cell proliferation, cell growth, and cell survival. Importantly, alleles of LKB1, a serine/threonine kinase that functions as a tumor suppressor, are somatically inactivated in ~30% of NSCLCs within KRAS-mutant NSCLC. The loss of LKB1 gives rise to aggressive, highly metastatic, and highly drug resistant tumors. We have previously demonstrated that the inactivation of the tumor suppressor lkb1 rendered mutant kras murine NSCLC resistant to targeted agents including BET bromodomain and kinase inhibitors.…
In vitro effect of cadmium and copper on separated blood leukocytes of Dicentrarchus labrax.
2013
The immunotoxic effects of heavy metals on blood leukocytes of sea bass (Dicentrarchus labrax) were examined. The cells, separated by a discontinuous Percoll-gradients, were exposed in vitro to various sublethal concentrations of cadmium and copper (10(-7) M, 10(-5) M, and 10(-3) M) and their immunotoxic effect was then evaluated by measuring neutral red uptake, MU assay, DNA fragmentation and Hsp70 gene expression. First of all, we demonstrated that the cells treated in vitro could incorporate Cd and Cu. A relationship between heavy metal exposure and dose-time-dependent alterations in responses of leukocytes from blood was found for both metals, but copper was more immunotoxic than cadmiu…
The effect of the great recession on foreign direct investment: global empirical evidence with a gravity approach
2013
This article estimates the effect of the present global systemic banking crisis on foreign direct investment (FDI) using the gravity equation on a sample of 161 countries over the period 2003 to 2010. Systemic banking crises, through demand shocks and credit constraints, may impact FDI in two ways: aggregate monetary flows and individual projects count. Since gravity equations account for output variations, our research relies on the financial constraints channel. We find that the great recession, through credit constraints on home supply markets, has reduced the number of FDI projects, but not their size, forcing investors to become more selective on their international endeavours.
Structural reforms in a debt overhang
2014
We assess the effects of reforms in product and labor markets in a model economy featuring credit restrictions and pre-existing long-term debt. Both elements, which are core features of the current scenario faced by some euro area countries, combine to produce a slow and protracted deleveraging of the private sector and a persistent recession following a negative financial shock. In this environment, we show that product and labor market reforms may stimulate output and employment even in the short run, despite their defl ationary effects. Furthermore, by favoring a faster recovery of investment and collateral values, product market reforms bring forward the end of deleveraging and the exit…
Stabilization effects of social spending: Empirical evidence from a panel of OECD countries
2010
Abstract The aim of this paper is to assess the ability of social spending to smooth output shocks and to provide stabilization. The results show that overall social spending is able to smooth about 15 percent of a shock to GDP. Among its sub-categories, social spending devoted to Old Age, Health and Unemployment are those that contribute more to provide smoothing. Moreover, the stabilization effects of social spending are significantly larger in those countries where the size of social spending is higher, and in countries in which social spending is less volatile. The empirical results are economically and statistically significant, and robust.
The Hsc/Hsp70 Co-Chaperone Network Controls Antigen Aggregation and Presentation during Maturation of Professional Antigen Presenting Cells
2011
The maturation of mouse macrophages and dendritic cells involves the transient deposition of ubiquitylated proteins in the form of dendritic cell aggresome-like induced structures (DALIS). Transient DALIS formation was used here as a paradigm to study how mammalian cells influence the formation and disassembly of protein aggregates through alterations of their proteostasis machinery. Co-chaperones that modulate the interplay of Hsc70 and Hsp70 with the ubiquitin-proteasome system (UPS) and the autophagosome-lysosome pathway emerged as key regulators of this process. The chaperone-associated ubiquitin ligase CHIP and the ubiquitin-domain protein BAG-1 are essential for DALIS formation in mou…
Metal complexes of phenobarbituric acid. Chelating behavior of the phenobarbiturate ring. Anticonvulsant properties of the K2[Cu(N-methylphenobarbitu…
1992
Abstract Na2Ni(phenobarbiturato)4·3H2O, Na2Ni3(phenobarbiturato)2(OH)6·4H2O, and NaZn(phenobarbiturato)2(OH)·H2O derivatives were prepared from Ni(II) and Zn(II) and phenobarbital. The Na2Ni(phenobarbiturato)4·3H2O complex is diamagnetic and isostructural with the complex previously reported, Na2Cu(phenobarbiturato)4, suggesting a square-planar environment around the Ni(II) ion. The DMF solutions of this complex show the existence of two species. The EPR spectra of the Cu(II) doped complex show the hyperfine and superhyperfine structures. The covalence parameters α2, β2, and δ2 show a strong bonding in the equatorial plane and suggests the formation of a [CuN4] chromophore. The anticonvulsa…