1,721,063 research outputs found
Early modifications of nucleic acid metabolism and nuclear lipid biosynthesis associated with antiproliferative activity of interferon-alpha on Daudi lymphoma cells.
No full textThe effect of human recombinant DNA interferon-alpha type A (rIFN alpha A) on nuclear lipid biosynthesis and on in vitro nucleic acid synthesis was investigated in Daudi lymphoma cells sensitive (Daudi Is) or resistant (Daudi Ir) to the antiproliferative activity of this glycoprotein. In the Daudi Is studied at 90 min and up to 8 h, relative proportions of 3H-labeled nuclear lipids were reproducibly altered as compared to controls: phosphatidylcholine increased while phosphatidylserine and total neutral lipids decreased. These changes were not detected in parallel studies of the whole cell extracts. No significant changes in the profiles of nuclear lipids were observed in Daudi Ir. Decreased rates of alpha DNA polymerase and of RNA transcription were evident within 90 min in the Daudi Is nuclei but not in untreated controls or nuclei from rIFN alpha A-treated Daudi Ir cells, thus suggesting a possible relationship of the rapid alterations of nuclear lipid biosynthesis in Daudi Is cells to the rIFN alpha A antiproliferative activity
Interferon alpha modulates phosphatidylinositol-3-kinase expression and distribution in Daudi lymphoma cells
No full textNucleolar morphological rearrangement related to transcriptional and replicative state in Burkitt lymphoma cells.
No full textThe specific silver staining of nucleolar region organizers was applied to Daudi lymphoma control and interferon alpha-treated cells. Isolated nuclei from control and treated samples were used for the kinetic analysis of in vitro RNA and DNA synthesis. Results have shown that interferon treatment induces a reduction of the transcriptional and replicative activities within 90 min. Concomitant to these results is the modification of the organization of nucleoli. Intensity and distribution of silver grains are, in fact, different in treated cells nucleoli as compared to those of controls. Thus, the number and the arrangement of granules could be related to the functional state of the cells suggesting that the transient cascade of interferon-generated signals involves also modulation of nucleolar structure and function in accordance with the hypothesis of a relationship of cell proliferation rate to silver-stained nucleolar protein quantity
Shift of DNA polymerase alpha nuclear distribution and activity in apoptotic human leukaemia cells.
No full textThe changes in the distribution of DNA polymerase alpha in nuclei from HL-60 cells treated with Methotrexate (MTX) for up to 15 hr. were checked by means of both confocal analysis and electron microscopy analysis. The results provided evidence that, relative to controls, in the MTX treated cells the enzyme undergoes a topographical rearrangement throughout the nucleus, showing a pattern of distribution which calls to mind the nuclear matrix structure. The "in vitro" analysis of DNA polymerases alpha, beta, and gamma activities revealed that, in nuclei from control cells, DNA polymerase alpha was the principal DNA polymerase driving this "in vitro" system, while after 15 hr. of MTX treatment its activity was largely decreased and replaced by DNA polymerase beta, which is believed to be associated with DNA repair. Taken together, these results suggest that among the intracellular processes elicited by MTX-induced apoptosis in HL60 cells, the redistribution of DNA polymerase alpha and the stimulation of DNA polymerase beta activity might represent an extreme attempt of the cell to preserve the replicative machinery during fragmentation and chromatin margination
Influence of phosphatidylcholine on two protein mRNA levels in interferon treated Daudi cells.
No full textEvidence related to nuclear structure and metabolism have shown the presence of a chromatin lipid fraction which may be involved in the events of cell proliferation and differentiation (Maraldi et al., 1984, Cocco et al., 1987). The relative amounts of these molecules have been reported to be modified in different metabolic conditions of normal and neoplastic cells (Coetzee et al., 1975; Manzoli et al., 1982). Phospholipids have also been found among the components of the nuclear matrix where they seem to play a role in the interactions between nucleic acids and proteins (Berezney, 1984; Cocco et al., 1987). In this paper we report that the transcriptional induction of two genes (pIFN-IND-1 and pIFN-IND-2) produced by interferon in Daudi lymphoma cells is influenced by addition, in the transcriptional assay, of phosphatidylcholine (PC) liposomes which have been reported to be able to enter nuclei (Maraldi et al., 1984; Maraldi et al., 1982)
Nutlins and Ionizing Radiation in Cancer Therapy
No full textRadioresistance stands as a fundamental barrier that limits the effectiveness of radiotherapy in cancer treatment. Recent evidences suggest that radioresistance is due to tumour repopulation and involves several signalling pathways, including p53/MDM2 interaction. Ionizing radiation induces p53-dependent MDM2 gene transcription that, in turn, inhibits p53 transcriptional activity, favouring its nuclear export and stimulating its degradation. In light of the observation that in many human tumours the inadequate function of p53 is the result of MDM2 over-expression, several authors have considered as an attractive therapeutic strategy to activate p53 signalling in tumours by inhibiting MDM2 activities or p53/MDM2 interaction. We retain that, by preventing the interaction p53/MDM2 with Nutlin, a small molecule that binds at the interface between these two proteins, the effectiveness of ionizing radiation treatment could be improved. Promising results have recently emerged from in vitro studies performed on laryngeal, prostate and lung cancer cell lines treated with Nutlin in combination with ionizing radiation. Based on these findings, we believe that the combined approach Nutlin/ionizing radiation should be further investigated for efficacy on both solid tumours and lymphoproliferative disorders as well as for side effects on normal cells and tissues. Therefore, the purpose of this review is to report the first results obtained by using Nutlins alone or in combination with other therapeutic agents on primary tumour cells, in vitro cell lines or tumour xenografts and to present the most recent advances in the understanding of the molecular mechanisms underlining ionizing radiation cytotoxicity and resistance
The Link Among Neurological Diseases: Extracellular Vesicles as a Possible Brain Injury Footprint
No full textExtracellular vesicles (EVs), referred as membranous vesicles released into body fluids from all cell types, represent a novel model to explain some aspects of the inter-cellular cross talk. It has been demonstrated that the EVs modify the phenotype of target cells, acting through a large spectrum of mechanisms. In the central nervous system, the EVs are responsible of the wide range of physiological processes required for normal brain function and neuronal support, such as immune signaling, cellular proliferation, differentiation, and senescence. Growing evidences link the EV functions to the pathogenic machinery of the neurological diseases, contributing to the disease progression and spreading. Extracellular vesicles are involved in the brain injury by multimodal ways; they propagate inflammation across the blood brain barrier (BBB), mediate neuroprotection and modulate regenerative processes. For these reasons, extracellular vesicles represent a promising biomarker in neurological disorders as well as an interesting starting point for the development of novel therapeutic strategies. Herein, we review the role of the EVs in the pathogenesis of neurological disease, discussing their potential clinical applications
Relationship between nuclear ribonucleoprotein arrangement and cell proliferation in Burkitt lymphoma cells.
No full textThe presence of body-like structures in nuclei from interferon alpha-treated Daudi cells has been shown on the ultrastructural level, by the use of different staining methods. The degree of their rearrangement in the nucleoplasm seems to be dependent on the time of interferon treatment. Since this morphological evidence has been found to be preceded by a slowing down of RNA transcriptional machinery early upon the interferon administration, it is speculated that interferon generated signals might lead to RNP granule accumulation in the nucleus and a consequent arrangement into defined structures
Analisi dei lipidi nucleari e dell'attività trascrizionale in cellule linfoblastoidi (Daudi) trattate sperimentalmente con Interferone
No full textAge-dependent variations in the expression of PLC isoforms upon mitogenic stimulation of peripheral blood T cells from healthy donors
No full textThe activation of phosphoinositide-specific phospholipase C (PLC) is one of the early responses to various growth factors and it is known that these functions are altered with ageing. In the present investigation, the expression and cellular distribution of PLC isoenzymes in immunocompetent T lymphocytes from a test group of healthy individuals over 65 years old and a comparison group of healthy donors below 30 years old were compared using Western blot and confocal microscopy. All lymphocyte samples responded biochemically to phytohaemagglutinin (PHA) stimulation, as shown by at least 10-fold increases in the beta(3) isoform and nuclear translocation of the beta(1), beta(2), beta(3), beta(4), gamma(1) and gamma(2) isoforms; however, consistent differences in the expression of the beta(2) isoform in unstimulated T cells and of the beta(2) and gamma(2) isoforms in stimulated T cells suggest that altered functions of the PLC pathway may have an age-dependent impact on signal transduction events
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