1,721,175 research outputs found
Oxygen supply" as modulator of aging processes: hypoxia and hyperoxia models for aging studies.
No full textCell growth is regulated by several factors, including oxygen supply, which influence cell metabolism. Aging is characterized by decreased oxygen supply to tissue, a reduction of tissue PO(2) and of the activity of several enzymes and metabolic factors. The oxygen-gradient diffusion at capillary tissue level is essential for the cellular survival, while the homeostasis of the oxygen in the arterial blood is mediated by reflexes sensitive to oxygen decrease and by release of several factors. Aging is correlated with a reduction of cells' oxygen supply concomitant to a parallel decrease in oxygen demand by tissues. Both chronic hypoxia or hyperoxia are considered as stresses. Indeed, in both conditions, free radical species, which damage structural and functional components of the membrane, are generated. ROS (reactive oxygen species) are physiological products of aerobic life and their accumulation affects aging. Because hypoxia per se modulates mitochondria activity, influencing oxygen consumption, hypoxia and aging could share some link. Moreover, the observation that in hypoxia or hyperoxia there is an accumulation of lipofucsine as a general reaction to stress is consistent with the accumulation of such components during aging. Correlation between hypoxia-hyperoxia and life-span remains open until we solve the question of how and why do cells sense oxygen. In other words, to better understand aging we need to know what O(2) species are being sensed by cells. In conclusion, hypoxia and hyperoxia represent an experimental model adequate for studying aging processes
Nucleolar 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)
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 textDiscovery of N-[2-(4-methylquinolin-2-yl)phenyl]acetamidine as a new potent nitric oxide synthase inhibitor against glioma progression
No full textGliomas are aggressive brain tumors with limited treatment options, often leading to poor patient outcomes despite surgery, radiation, and chemotherapy. Current therapies, such as temozolomide and radiation, provide only temporary control, as gliomas frequently develop resistance. Therefore, there is an urgent need for new therapeutics to improve survival and quality of life for patients. In the present study, we explore the hypothesis that the dual inhibition of both the neuronal and inducible nitric oxide synthases could represent a promising therapeutic approach, being these two enzymes often dysregulated in gliomas. To this end, the new quinoline-based compound 3 was synthetized by a simple, innovative and solvent-free procedure. The molecule was a potent dual inhibitor and demonstrated significant antitumor activity against glioma, both as a monotherapy and in combination with temozolomide
Age-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
Influence of phenol red on Protein Kinase C alpha mediated stress response to HEMA in human female gingival fibroblasts
No full textCytotoxicity and apoptosis induction by e-cigarette fluids in human gingival fibroblasts
No full textElectronic cigarettes (e-cigarettes) are generally acknowledged as a safer alternative to the use of combusted tobacco products. Nevertheless, there are increasing conflicting claims concerning the effect of these novel industrial products on the health of e-cigarettes users. The aim of this work was to investigate the effects of the liquids of e-cigarettes on human gingival fibroblasts (HGFs) and to compare the effects of nicotine-containing fluid to the fluid itself. HGFs were treated with different concentrations (0-5 mg/mL) of fluids of e-cigarettes for different times (0-72 h) and cytotoxicity was analyzed by MTT assay. Fluids were administered also after being vaped (e.g., warmed into the cartomizer). Apoptosis occurrence and Bax expression were evaluated by flow cytometry; ROS production was analyzed by fluorescence optical microscopy. Both nicotine-containing and nicotine-free fluids induced an increased ROS production after 24 h, along with an increased Bax expression, followed by apoptosis occurrence after 48 h of exposure. The cytotoxicity exerted on HGFs by e-cigarettes fluids is not entirely ascribable to nicotine. Since the e-cigarettes are advertised as a safer alternative to traditional ones, especially for the possibility of "smoking" nicotine-free fluids, further studies are necessary to clarify the mechanism involved in the occurrence of cytotoxicity exerted by such compounds. Our results suggest a role for e-cigarette fluids in the pathogenesis of oral diseases, such as periodontitis
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