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Biomedical subjects

V Chiarugi

Publications and source records attributed to V Chiarugi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dominant oncogenes, tumor suppressors, and radiosensitivity.

A variety of conflicting results appeared in the literature concerning the effect of dominant oncogenes on the sensitivity to irradiation and to anticancer agents in a number of cell lines of human and animal origin. In this report we provide evidence supporting the hypothesis that the tumor suppressor gene p53 and the apoptosis suppressor gene bcl2 modulate the effect of dominant oncogenes and that the effect of dominant oncogenes on resistance or sensitivity is dependent on the balance between the expression of p53 and bcl2.

Apoptosis↗
PubMed1994

Apoptosis and the cell cycle.

This brief review examines the strict relationships between cell apoptosis and G1 cyclins. It has been shown that the basic role of G1 cyclins is in regulating G1 progression and G1/S transition (the critical cycle point for cell program decisions, including apoptosis) a fatal program for cells unable to bypass G1/S checkpoint 1. Notably, both of the two giant regulators of checkpoint 1 (i.e., p105RB [retinoblastoma oncosuppressor-encoded protein] and p53 dependent WAF1/CIP1) are influenced by or influence G1 cyclins: cyclin E/cdk2 kinase complexes hyperphosphorylate p105RB, induce E2F release, and free G1 exit. On the other hand, p21-WAF1/CIP1 is an inhibitor of cyclin-dependent kinases blocking cells at G1/S. Thus, G1 cyclin activity appears as a conditio sine qua non for G1 exit and apoptosis escape.

Animals↗
PubMed1993

Cytokine receptor signal transduction mechanisms in immuno-hematopoietic cells.

Novel aspects of cytokine receptor signal transduction are discussed and cytokine receptors classified based on ligand-dependent signalling. An introductory section presents an overview of the role of cytokines in hematopoiesis. A brief explanation of basic concepts, such as redundancy, pleiotropy, synergism, etc., important for the understanding of cell response to cytokines, is also included. Three of five classes of receptors show the involvement of tyrosine kinase activity as the key step in signal transduction. The importance of tyrosine phosphorylation in cellular response to cytokines is pointed out.

Animals↗
PubMed1990

Transformation by ras oncogene induces nuclear shift of protein kinase C.

We measured protein kinase C (PKC) activity in normal and ras-transformed Balb/3T3 fibroblasts; cytosolic and nuclear-associated PKC activity was determined either as phorbol ester binding, PKC-dependent phosphorylation of histone III-S, or phosphorylation of endogenous nuclear proteins. Results demonstrate that ras-transformed fibroblasts show down-regulation of cytosolic PKC accompanied by increase of nuclear-associated PKC. These results provide evidence linking transformation to PKC nuclear shift with consequent phosphorylation of nuclear proteins.

Animals↗
PubMed1990

Interaction between endogenous circulating sulfated-glycosaminoglycans and plasma proteins.

Interaction between endogenous 35S-labelled plasma glycosaminoglycans and proteins in murine plasma was demonstrated by coelution from gel chromatography of circulating 35S-labelled glycosaminoglycans with a wide range of plasma proteins. Autoradiography of electrophoretic tracing of proteins from 35S-sulfate labelled plasma showed that labelled glycosaminoglycans were associated with alpha 1, alpha 2, beta globulins and albumin, but not with gamma globulins. Analysis by gel chromatography on Sepharose CL-6B of delipidated 35S-labelled plasma after either proteolysis or beta-elimination, suggested that 35S-labelled glycosaminoglycan chains were covalently bound to proteins. Lipids were probably involved in the supramolecular assembly of GAGs with plasma proteins, as shown by hydrophobic interaction chromatography. In addition, strong, non-covalent interaction between glycosaminoglycan chains and proteins was responsible for the difficulty in extracting 'free' glycosaminoglycans from plasma. Consistently, ion-exchange chromatography of 35S-sulfate labelled delipidated plasma after alkali treatment, revealed that the anionic properties of glycosaminoglycans were hampered when plasma proteins were present.

Animals↗
PubMed1989

Synthesis of diacylglycerol de novo is responsible for permanent activation and down-regulation of protein kinase C in transformed cells.

We measured the synthesis of diacylglycerol de novo in normal NIH/3T3 fibroblasts and in cells transformed by ras, src, sis and abl oncogenes. Analysis of the incorporation of glucose-derived 14C into diacylglycerol indicated that neosynthesis of diacylglycerol was constitutively active in the transformed cell lines. Elevated levels of diacylglycerol and persistent activation/down-regulation of protein kinase C reduced the binding of phorbol dibutyrate to transformed cells. This phenomenon could be reversed by blocking the glycolytic pathway, thus indicating that neosynthesized diacylglycerol was responsible for persistent activation and down-regulation of protein kinase C. In transformed cells, protein kinase C activity could not be stimulated by the addition of diolein; however, inhibition of glycolysis restored the ability of transformed cells to respond to diolein. Taken together these data indicate that constitutive synthesis of diacylglycerol de novo is responsible for activation and down-regulation of protein kinase C in transformed cells, and it may play a role in altered mitogenic signalling.

Animals↗
PubMed1988

Effect of exogenously added acylphosphatases on inositol lipid metabolism in human platelets.

In this paper we demonstrate that human platelets contain an acylphosphatase isoenzyme. We then investigated the effect of exogenously added human muscle and erythrocyte acylphosphatases on inositol lipid content in human platelets permeabilized with saponin. Alterations in the level of the polyphosphoinositides were observed: in particular, the levels of phosphatidylinositol 4,5-bisphosphate, and of phosphatidylinositol 4-monophosphate were decreased, whereas the level of phosphatidylinositol was increased. These results suggest that acylphosphatases promote polyphosphoinositide dephosphorylation, possibly through intracellular Ca2+ mobilization.

Acid Anhydride Hydrolases↗
PubMed1988

Binding, internalization and degradation of heparin and heparin fragments by cultured endothelial cells.

We have studied the binding to bovine adrenal capillary endothelial cells cultured in vitro of heparin from different sources (porcine heparin Ep. 152 P, Av.M.W. 15.9 Kd and bovine heparin Ep. 756 P, Av.M.W. 12.9 Kd) and heparin fractions of various molecular weights (low molecular weight heparin, LMW 2123 OP, Av.M.W. 4.5 Kd and very low molecular weight heparin, VLMW 1027/45 OP Av.M.W. 2.1 Kd). The binding was specific for heparin; heparan sulphate showed some competition whereas dextran sulphate and glycosaminoglycans did not. We determined the affinity of heparin and heparin fragments for endothelial cells by means of displacement of bound 3H-labeled heparin in response to increasing concentration of unlabeled compounds. The binding of the different heparin fractions depends on their molecular weights. VLMW 1027/45 OP was unable to bind to the cells, whereas LMW 2123 OP showed an affinity 10 times lower then porcine heparin. Bovine adrenal capillary endothelial cells incubated with unfractionated 3H-labeled heparin selectively bound internalized and degraded high molecular weight heparin fractions, as shown by gel filtration of the 3H-labeled heparin both after binding to the cells and after internalization.

Adrenal Glands↗
PubMed1987

Molecular mechanism underlying impaired platelet responsiveness in liver cirrhosis.

We have studied platelet function in 10 patients with severe liver cirrhosis, compared to healthy subjects. Using washed platelets, we have investigated the molecular mechanism underlying the defect in platelet aggregation frequently observed in these patients. We have found that platelets from cirrhotic patients have a reduced responsiveness to thrombin and collagen in terms of aggregation, and receptor-dependent activation of phospholipase C, A2 and cyclooxygenase/thromboxane synthetase. We thus suggest that this impairment in transmembrane signalling is responsible for the defective platelet function observed in cirrhosis.

Adult↗
PubMed1987

Phospholipase C activation induced by noradrenaline in rat hippocampal slices is potentiated by GABA-receptor stimulation.

We have studied the effect of gamma-aminobutyric acid (GABA) and other GABA-receptor agonists (3-aminopropanesulphonic acid and muscimol) on the noradrenaline-induced stimulation of polyphosphoinositide metabolism in rat hippocampal slices. Formation of water-soluble inositol phosphates, and polyphosphoinositide metabolism were studied in hippocampal slices prelabelled with [3H]myoinositol. Noradrenaline induced formation of inositol mono-, bis- and trisphosphate during 10 min incubation in the presence of lithium; activation of phospholipase C by noradrenaline was also reflected by the hydrolysis of polyphosphoinositides and by the increased metabolism of phosphatidylinositol. GABA-receptor agonists were unable to activate per se phospholipase C; however, when added together with a low concentration of noradrenaline, they greatly potentiated the noradrenaline-stimulated polyphosphoinositide metabolism. We conclude that GABA-receptor agonists potentiate the effect of noradrenaline on polyphosphoinositide turnover and we discuss the role of this neurotransmitter interaction in the physiology of the hippocampus.

Animals↗
PubMed1987

Polyphosphoinositide metabolism is rapidly stimulated by activation of a temperature-sensitive mutant of Rous sarcoma virus in rat fibroblasts.

We have examined polyphosphoinositide turnover in a Rat-1 fibroblast line infected with a temperature-sensitive mutant (ts LA24) of the Rous sarcoma virus (RSV). When ts LA24-infected cells are shifted from the non-permissive to the permissive temperature, a rapid and sustained activation of phospholipase C (PLC) is observed. Normal and wild-type RSV-infected Rat-1 cells do not show any PLC activation upon temperature shiftdown. Pre-treatment of ts LA24-infected fibroblasts with tetrodotoxin (a Na+ channel inhibitor) or incubation in Na+-free medium significantly prevent temperature shiftdown-induced PLC activation. Therefore, we conclude that PLC activation occurs concomitantly with pp60v-src expression, and hypothesize that pp60v-src-related membrane depolarization is the causal link between pp60v-src tyrosine kinase activity and stimulation of polyphosphoinositide metabolism. Finally, we discuss the relationship between the phenomena we have observed and the mechanism of action of the ras oncogene.

Animals↗
PubMed1986

Internalization and metabolism of endogenous heparin by cultured endothelial cells.

We have studied the ability of bovine adrenal capillary cells cultured in vitro to uptake and metabolize heparin. We have previously demonstrated that endogenous heparin can be extracted from human plasma (Vannucchi, S. et al., (1985) Biochem. J. 227, 57-65), and here we show that also endothelial cells contain heparin. However, experiments with (35S)sodium sulfate labeling indicate that these cells do not synthesize de novo heparin, but they uptake it from culture serum. Bovine adrenal capillary endothelial cells are able to bind and uptake (3H)heparin added to culture medium and they also release its low molecular weight degradation products, thus indicating a metabolism of heparin. We discuss about the role of endothelial cell-mediated uptake and metabolism of endogenous heparin in relationship with circulating heparin. We also discuss about these events as related to some of the antithrombogenic properties of the endothelium.

Animals↗
PubMed1986

Cooperation of heparin with other angiogenetic effectors.

The heterogeneous variety of factors involved in the induction of vessels to proliferate is briefly reviewed in connection with the possible cooperative role of heparin, a compound indicated by many kinds of evidence to be basically involved in angiogenesis.

Adenosine Diphosphate↗
PubMed1985

Transformation of BALB/3T3 cells with EJ/T24/H-ras oncogene inhibits adenylate cyclase response to beta-adrenergic agonist while increases muscarinic receptor dependent hydrolysis of inositol lipids.

Balb/3T3 murine fibroblasts transformed by transfection with the EJ/T24 human bladder carcinoma oncogene were assayed in terms of adenylate cyclase response and hydrolysis of polyphosphoinositides dependent on specific agents. Transformed cells were much less responsive to beta-adrenergic agonists in rising cAMP than normal cells. They are instead much more sensitive to muscarinic receptor agonists, inducing a rapid intracellular accumulation of inositol phosphates. These results suggest that the functional alteration of the cell membrane caused by the product of the point mutated H-ras oncogene concerns in 3T3 fibroblasts both inhibitory and stimulatory effects, respectively on adenylate cyclase and phosphoinositide-phosphodiesterase.

Adenylyl Cyclases↗