Biomedical subjects

G Sorci

Publications and source records attributed to G Sorci.

18 recordsLinked to original sources

PubMed2006

S100B protects LAN-5 neuroblastoma cells against Abeta amyloid-induced neurotoxicity via RAGE engagement at low doses but increases Abeta amyloid neurotoxicity at high doses.

At the concentrations normally found in the brain extracellular space the glial-derived protein, S100B, protects neurons against neurotoxic agents by interacting with the receptor for advanced glycation end products (RAGE). It is known that at relatively high concentrations S100B is neurotoxic causing neuronal death via excessive stimulation of RAGE. S100B is detected within senile plaques in Alzheimer's disease, where its role is unknown. The present study was undertaken to evaluate a putative neuroprotective role of S100B against Abeta amyloid-induced neurotoxicity. We treated LAN-5 neuroblastoma cultures with toxic amounts of Abeta25-35 amyloid peptide. Our results show that at nanomolar concentrations S100B protects cells against Abeta-mediated cytotoxicity, as assessed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein isothiocyanate nick end-labeling (TUNEL) experiments, by countering the Abeta-mediated decrease in the expression of the anti-apoptotic factor Bcl-2. This effect depends on S100B binding to RAGE because S100B is unable to contrast Abeta-mediated neurotoxicity in neurons overexpressing a signaling-deficient RAGE mutant lacking the cytosolic and transducing domain. Our data suggest that at nanomolar doses S100B counteracts Abeta peptide neurotoxicity in a RAGE-mediated manner. However, at micromolar doses S100B is toxic to LAN-5 cells and its toxicity adds to that of the Abeta peptide, suggesting that additional molecular mechanisms may be involved in the neurotoxic process.

Amyloid beta-Peptides↗

PubMed2002

Does beak coloration of male blackbirds play a role in intra and/or intersexual selection?

In many bird species, males may show brightly coloured traits and variance in male mating success may be explained by female preference and/or competition between males favouring the most coloured males. Male beak coloration has been suggested to play an important role in the pairing pattern of European blackbirds. Here, we investigate female preference and male-male interactions in relation to male beak coloration in this species. We used a field experiment to measure female and male responses toward stuffed decoys showing either of two beak coloration representing the extremes of the natural variation from yellow to orange. Decoys were situated on the centre of plots and behaviours of males and females approaching the decoy were recorded. The total number of males and females approaching the decoy did not differ between the two model treatments. Similarly, there was no difference in the mean time that males and females spent near the decoy. The number of males displaying aggressive postures did not differ between treatments and no female adopted a sexual posture. We discuss the relevance of our results and potential limitations associated with the experimental procedure.

Journal Article↗

PubMed2001

S100B expression in and effects on microglia.

We evaluated the intracellular and extracellular biological role of S100B protein with respect to microglia. S100B, which belongs to the multigenic family of Ca2+-binding proteins, is abundant in astrocytes where it is found diffusely in the cytoplasm and is associated with membranes and cytoskeleton constituents. S100B protein is also secreted by astrocytes and acts on these cells to stimulate nitric oxide secretion in an autocrine manner. However, little is known about the relationship between S100B and microglia. To address this issue, we used primary microglia from newborn rat cortex and the BV-2 microglial cell line, a well-established cell model for the study of microglial properties. S100B expression was assessed by immunofluorescence in primary microglia and by RT-PCR, Western blotting, and immunofluorescence in BV-2 cells. S100B was found in microglia in the form of a filamentous network as well as diffusely in the cytoplasm and associated with intracellular membranes. S100B relocated around phagosomes during BV-2 phagocytosis of opsonized Cryptococcus neoformans. Furthermore, interferon-gamma (IFN-gamma) treatment caused cell shape changes and redistribution of S100B, and downregulation of S100B mRNA expression in BV-2 cells. Treatment of BV-2 cells with nanomolar to micromolar amounts of S100B resulted in increased IFN-gamma-induced expression of inducible nitric oxide synthase mRNA as well as nitric oxide secretion. Taken together, these data suggest a possible role for S100B in the accomplishment/regulation of microglial cell functions.

Animals↗

PubMed2000

Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation.

Amphoterin is a protein enhancing process extension and migration in embryonic neurons and in tumor cells through binding to receptor for advanced glycation end products (RAGE), a multiligand transmembrane receptor. S100 proteins, especially S100B, are abundantly expressed in the nervous system and are suggested to function as cytokines with both neurotrophic and neurotoxic effects. However, the cell surface receptor for the cytokine function of S100B has not been identified. Here we show that two S100 family proteins, S100B and S100A1, activate RAGE in concert with amphoterin inducing neurite outgrowth and activation of transcription factor NF-kappaB. Furthermore, activation of RAGE by amphoterin and S100B promotes cell survival through increased expression of the anti-apoptotic protein Bcl-2. However, whereas nanomolar concentrations of S100B induce trophic effects in RAGE-expressing cells, micromolar concentrations of S100B induce apoptosis in an oxidant-dependent manner. Both trophic and toxic effects are specific for cells expressing full-length RAGE since cells expressing a cytoplasmic domain deletion mutant of RAGE are unresponsive to these stimuli. These findings suggest that activation of RAGE by multiple ligands is able to promote trophic effects whereas hyperactivation of RAGE signaling pathways promotes apoptosis. We suggest that RAGE is a signal-transducing receptor for both trophic and toxic effects of S100B.

Animals↗

PubMed2000

Effects of S100A1 and S100B on microtubule stability. An in vitro study using triton-cytoskeletons from astrocyte and myoblast cell lines.

S100A1 and S100B are members of a multigenic family of Ca(2+)-binding proteins of the EF-hand type highly abundant in astrocyte and striated muscle cells that have been implicated in the Ca(2+)-dependent regulation of several intracellular activities including the assembly and disassembly of microtubules and type III intermediate filaments. In the present work we tested S100A1 and S100B for their ability to cause microtubule and/or intermediate filament disassembly in situ using triton-cytoskeletons obtained from U251 glioma cells and rat L6 myoblasts. Our results indicate that: (i) both proteins cause a Ca(2+)-dependent disassembly of cytoplasmic microtubules in a dose-dependent manner; (ii) the S100A1- and S100B-inhibitory peptide, TRTK-12, blocks the S100A1 and S100B effects on microtubules; (iii) S100A1Delta88-93, an S100A1 mutant lacking the C-terminal extension, does not affect microtubule stability; and (iv) no obvious S100A1- or S100B-dependent intermediate filament disassembly could be observed under the experimental conditions used in the present study, but S100A1- and S100B-dependent microtubule disassembly results in a tendency of vimentin intermediate filaments to aggregate into bundles and/or to condense. Together, these results suggest that S100A1 and S100B probably cause microtubule disassembly by interacting with the microtubule wall, and that the two proteins do not affect intermediate filament stability via interaction with preformed intermediate filaments, in agreement with previous biochemical investigation. Our present data lend support to the possibility that S100A1 and S100B might have a role in the in vivo regulation of the state of assembly of microtubules in a Ca(2+)-regulated manner and, potentially, on microtubule-based activities in astrocytes and myoblasts. Also, these data suggest that the both S100 proteins use their C-terminal extension for interacting with microtubules.

Animals↗

PubMed1999

Retaliatory cuckoos and the evolution of host resistance to brood parasites.

We present a dynamic model of the evolution of host resistance to avian brood parasites, when the latter can retaliate against hosts that reject parasitic eggs. In a verbal model, Zahavi (1979, American Naturalist, 113, 157-159) suggested that retaliatory cuckoos might prevent the evolution of host resistance by reducing the reproductive success of rejecter hosts (i.e. by destroying their eggs or nestlings). Here we develop a model based on the association between the great spotted cuckoo, Clamator glandarius, and its main host, the European magpie, Pica pica, because this is the only system that has provided supportive evidence, to date, for the existence of retaliatory behaviour. Our aims were (1) to derive the conditions for invasion of the retaliation strategy in a nonretaliatory parasite population and (2) to investigate the consequences of retaliation for the evolution of host defence. If we assume a cost of discrimination for rejecter hosts in the absence of parasitism, and a cost paid by a retaliator for monitoring nests, our model shows cyclical dynamics. There is no evolutionarily stable strategy, and populations of both hosts and parasites will cycle indefinitely, the period of the cycles depending on mutation and/or migration rate. A stable polymorphism of acceptors and rejecters occurs only when parasites are nonretaliators. The spread of retaliator parasites drives rejecter hosts to extinction. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed1999

Regulation of the p75 neurotrophin receptor in a rat myogenic cell line (L6).

Neurotrophins are expressed in muscle cells both during development and postnatally. Furthermore, during development muscle cells express high levels of the common p75 neurotrophin receptor, which binds all neurotrophins. Only fragmentary and controversial data are available regarding the responsiveness of muscle cells to neurotrophins and the importance of low-affinity p75 receptor in muscle development. The present study investigates in vitro the immunocytochemical expression of p75 in a rat myogenic cell line (L6) at various time points and in response to different coating substrates as a first step in elucidating the regulation of p75 in muscle. We found that in L6 myoblasts, p75 is expressed only at very early stages of maturation and its levels of expression are regulated by the nature of the coating substrates. p75 expression decreases in cells growing on substrates more suitable for myoblast fusion into myotubes. Time course analysis indicates a reverse correlation between myoblast fusion into myotubes and the levels of p75 expression. Myotubes were always p75 negative. Substrates not suitable for the fusion process induced a prolonged presence of p75 in myoblasts with an increase of their apoptosis. We conclude that expression of p75, at least in this in vitro condition, is regulated by the stages of myoblast differentiation and the nature of the coating substrates. According to the observed time- and substrate-related evidences, future studies should investigate in vivo both the regulation of p75 in the myoblast fusion and the effects and the importance of neurotrophins binding during myoblast differentiation.

Animals↗

PubMed1999

Replicating myoblasts and fused myotubes express the calcium-regulated proteins S100A1 and S100B.

We investigated the expression and the subcellular localization of S100A1 and S100B, two Ca(2+)-binding proteins of the EF-hand type, in replicating myoblasts and fused myotubes. Northern blot and reverse transcriptase-polymerase chain reaction analyses revealed the presence of S100A1 mRNA and S100B mRNA respectively, in myoblasts. Immunofluorescence and immunogold electron microscopy were used to localize individual proteins in myoblasts and myotubes. In the present report we document that: (1) in replicating myoblasts S100B is localized to intracellular membranes, including Golgi membranes, vimentin intermediate filaments (IFs) and microtubule (MT) structures; (2) in the same cells S100A1 is found associated with intracellular membranes; (3) following treatment of replicating myoblasts with colchicine, a fraction of S100B remains colocalized with bundled and collapsed vimentin IFs, whereas another fraction follows the destiny of endoplasmic membranes; (4) under the same conditions S100A1, like a fraction of S100B, follows the collapse of the endoplasmic reticulum around the nucleus; and (5) in fused myotubes S100A1 is found diffusely in the cytoplasm, whereas S100B is mostly found associated with vimentin IFs. These data suggest that in the skeletal myogenic cell line used in the present study S100A1 and S100B might share binding sites on or close to intracellular membranes, but display a significant degree of target specificity with respect of IFs and MTs. The results of these analyses suggest that expression of S100B in skeletal muscle cells may be developmentally regulated and lend support to the possibility that S100B might regulate the MT and IF dynamics.

Amino Acid Sequence↗

PubMed1999

The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments.

The Ca2+-modulated, dimeric proteins of the EF-hand (helix-loop-helix) type, S100A1 and S100B, that have been shown to inhibit microtubule (MT) protein assembly and to promote MT disassembly, interact with the type III intermediate filament (IF) subunits, desmin and glial fibrillary acidic protein (GFAP), with a stoichiometry of 2 mol of IF subunit/mol of S100A1 or S100B dimer and an affinity of 0.5-1.0 microM in the presence of a few micromolar concentrations of Ca2+. Binding of S100A1 and S100B results in inhibition of desmin and GFAP assemblies into IFs and stimulation of the disassembly of preformed desmin and GFAP IFs. S100A1 and S100B interact with a stretch of residues in the N-terminal (head) domain of desmin and GFAP, thereby blocking the head-to-tail process of IF elongation. The C-terminal extension of S100A1 (and, likely, S100B) represents a critical part of the site that recognizes desmin and GFAP. S100B is localized to IFs within cells, suggesting that it might have a role in remodeling IFs upon elevation of cytosolic Ca2+ concentration by avoiding excess IF assembly and/or promoting IF disassembly in vivo. S100A1, that is not localized to IFs, might also play a role in the regulation of IF dynamics by binding to and sequestering unassembled IF subunits. Together, these observations suggest that S100A1 and S100B may be regarded as Ca2+-dependent regulators of the state of assembly of two important elements of the cytoskeleton, IFs and MTs, and, potentially, of MT- and IF-based activities.

Calcium↗

PubMed1998

Association of S100B with intermediate filaments and microtubules in glial cells.

Previous in vitro studies have shown that the Ca2+-regulated S100B protein modulates the assembly-disassembly of microtubules (MTs) and type III intermediate filaments (IFs). In the present report, by double immunofluorescence cytochemistry S 100B was localized to both GFAP/vimentin IFs and MTs as well as to centrosomes in U251 glial cells. In cells treated with the MT-depolymerizing agent, colchicine, S100B remained associated with the rearranged GFAP IFs throughout the cell and, at the cell periphery, vimentin IFs. In cells treated with the MT stabilizing agent, taxol, S100B followed partly the rearrangement of MTs and partly the rearrangement of IFs. Under the latter condition, bundles of MTs with their associated S100B appeared surrounded and/or flanked by rearranged IFs with their associated S100B. Colocalization of S100B with closely arranged IFs and MTs was best evident in cells manipulated with taxol and in triton-cytoskeletons. In these cases, MTs and their associated S100B appeared surrounded and/or flanked by and/or intermingled with IFs and their associated S100B. Also, a preferential association of S100B with GFAP vs. vimentin IFs could be observed near the nucleus where colocalization of S100B with MTs was also maximal. Condensation of IFs and alteration of the MT network caused by treatment of cells with the phosphatase inhibitor, okadaic acid, resulted in a concomitant condensation/alteration of the S100B immunoreactivity. The present results lend support to the possibility that S100B may be an important factor implicated in the regulation of the dynamics of MTs and IFs.

Calcium-Binding Proteins↗

PubMed1998

Determinants of Life-history Evolution in Nematodes.

What are the determinants of parasite life-history evolution? Does life-history evolution of parasitic species differ from their free-living relatives? How and why do host and parasite life-history traits covary? Here, Serge Morand and Gabriele Sorci use recent comparative studies to investigate life-history evolution in nematodes which present both parasitic and free-living groups. Application of life-history theory to nematodes suggests that the conventional wisdom concerning the high fecundity of parasitic species could simply be the result of the larger body size of the latter when compared with free-living forms. The authors also emphasize, with the use of examples, that in most cases parasite life-history evolution depends on host features.

Journal Article↗

PubMed1997

Host-parasite coevolution: comparative evidence for covariation of life history traits in primates and oxyurid parasites.

The environmental factors that drive the evolution of parasite life histories are mostly unknown. Given that hosts provide the principal environmental features parasites have to deal with, and given that these features (such as resource availability and immune responses) are well characterized by the life history of the host, we may expect natural selection to result in covariation between parasite and host life histories. Moreover, some parasites show a high degree of host specificity, and cladistic analyses have shown that host and parasite phylogenies can be highly congruent. These considerations suggest that parasite and host life histories may covary. The central argument in the theory of life history evolution concerns the existence of trade-offs between traits. For parasitic nematodes it has been shown that larger body sizes induce higher fecundity, but this is achieved at the expense of delayed maturity. As high adult mortality would select for reduced age at maturity, the selective benefit of increased fecundity is expressed only if adult mortality is low. Parasite adult mortality may depend on a number of factors, including host longevity. Here we tested the hypothesis concerning the positive covariation between parasite body size (which reflects parasite longevity) and host longevity. To achieve this goal, we used the association between the pinworms (Oxyuridae, Nematoda) and their primate hosts. Oxyurids are highly host specific and are supposed to be involved in a coevolutionary process with their hosts. We found that female parasite body length was positively correlated with host longevity after correcting for phylogeny and host body mass. Conversely, male parasite body length and host longevity were not correlated. These results confirm that host longevity may represent a constraint on the evolution of body size in oxyurids, at least in females. The discrepancy between female and male oxyurids is likely to depend on the particular mode of reproduction of this taxon (haplodiploidy), which should result in weak (or even null) selection pressures to an increase of body size in males.

Animals↗

PubMed1996

Patterns of haemogregarine load, aggregation and prevalence as a function of host age in the lizard Lacerta vivipara.

Patterns of haemogregarine load, aggregation, and prevalence as a function of host age in the lizard Lacerta vivipara were investigated. These parameters may provide evidence for the potential effect of parasites on host survival. The predictions of theoretical models concerning the shape of parasite load, parasite aggregation, and parasite prevalence across host age were used to test if parasites are a significant source of host mortality. Both age-intensity and age-aggregation curves were found to be peaked, whereas the age-prevalence curve increased with host age, reaching high levels (> 80% of infected hosts). These findings of humped age-aggregation and age-intensity curves are in good agreement with the predictions of the Anderson and Gordon (1982) model and suggest that haemogregarines may influence age-dependent host mortality in this population of L. vivipara.

Aging↗

PubMed1995

Detection of membrane-bound guanylate cyclase activity in rat C6 glioma cells at different growth states following activation by natriuretic peptides.

We studied the activity and the ultracytochemical localization of membrane-bound guanylate cyclase (GC) after stimulation with rat atrial natriuretic peptide (rANP), porcine brain natriuretic peptide (pBNP), rat brain natriuretic peptide (rBNP), or porcine C-type natriuretic peptide (CNP) in rat C6 glioma cells during proliferation or following exposure of confluent cells to dibutyryl cyclic AMP (db-cAMP) or retinoic acid (RA). Under our experimental conditions all peptides were activators of GC as demonstrated by the accumulation of cGMP within cells. During proliferation of C6 cells, the amounts of cGMP remained approximately constant. However, at subconfluency, confluency and postconfluency, the GC reaction product was located at different sites in C6 cells. At subconfluency, GC reaction product was on membranes of protoplasmic extensions, at postconfluency, GC reaction product was in association with membranes of cell bodies, and at confluency, both localizations of GC reaction product were detected. Incubation of confluent cells in culture medium containing db-cAMP or RA induced the appearance of long and slender protoplasmic extensions. Under these conditions, the GC reaction product was localized exclusively to these processes. These data suggest that GC is differentially located depending on the state of growth of glial cells, and that in differentiating glial cells GC is preferentially located in cell processes.

Animals↗

PubMed1995

Repeated measurements of blood parasite levels reveal limited ability for host recovery in the common lizard (Lacerta vivipara).

I investigated longitudinal measures of haemogregarine load in the host lizard Lacerta vivipara over 2 yr (1992-1993). Lizards with heavy parasite infections in 1992 were still suffering from heavy parasite infections in 1993. Such data show that lizards have limited ability to recover from high levels of haemogregarine infection. Modifications of host behavior and of life-history traits may represent a more effective and less costly response to haemogregarine infection in this species.

Animals↗

PubMed1993

Immunocytochemical analyses of annexin V (CaBP33) in a human-derived glioma cell line. Expression of annexin V depends on cellular growth state.

The subcellular distribution of annexin V, a calcium-dependent phospholipid- and membrane-binding protein, in a human-derived cell line, GL15, was investigated by immunocytochemistry at light and electron microscope levels. Annexin V was found diffusely in the cytoplasm and associated with plasma membranes, membranes delimiting cytoplasmic vacuoles, membranes of the endoplasmic reticulum, and filamentous structures the identity of which remains to be established. By immunocytochemistry at the light microscope level and immunochemistry, the expression of annexin V in these cells was found to depend on cellular growth stage, being maximal soon after plating and progressively declining thereafter. However, re-expression of annexin V was observed whenever cell proliferation slowed down or arrested. These findings suggest that annexin V in glioma cells is mostly expressed in connection with cell differentiation. Also, the present ultrastructural data suggest that plasma membranes, membranes of the endoplasmic reticulum and the cytoskeleton are prominent sites of action of annexin V in vivo, thus lending support to the possibility that this protein might have a role in the regulation of cytoskeleton elements and/or of the structural organization of membranes.

Animals↗

PubMed1991

'Neuron-specific' protein gene product 9.5 (PGP 9.5) is also expressed in glioma cell lines and its expression depends on cellular growth state.

Protein gene product 9.5 (PGP 9.5), which in the normal nervous system is restricted to certain neurons, has been detected in two glioma cell lines, rat C6 and human GL15, by immunoblotting and immunocytochemistry. Its expression in these cells depends on the cellular growth state, being maximal between the first and second post-plating day. Only a faint PGP 9.5 immunoreactivity can be observed in glioma cells after the eleventh post-plating day, i.e. about one week after confluency has been reached. The present results suggest that PGP 9.5 in cultured glial cells is maximally expressed during the growth phase and that the protein could play a role during brain development in glial cells, in reactive gliosis, or in tumorigenesis of the glial lineage.

Amino Acid Sequence↗

PubMedDate not supplied

Effect of recombinant murine tumor necrosis factor on the generation of natural killer cells in bone marrow cultures.

We investigated the possible role of tumor necrosis factor-alpha (TNF-alpha) in the interleukin-2 (IL-2)-dependent generation of natural killer (NK) cells from bone marrow precursors. TNF-alpha synergistically augmented both cytotoxic activity against NK-sensitive targets and cell number at the end of the 7-day incubation period. After this time, NK activity was not induced by TNF-alpha in the absence of IL-2. The cytotoxic cells generated by IL-2 + TNF-alpha had the phenotype of mature NK cells, including expression of NK-1.1, asialo-GM1, Ly-5, LFA-1 and Thy-1. TNF-alpha was also able to up-regulate the mRNA expression for the IL-2 receptor alpha-chain (P55) as well as the mRNA expression of c-myc protooncogene. Blocking studies with monoclonal antibodies against the alpha-chain P55 of the IL-2 receptor confirmed the functional role ascribed to IL-2 in the in vitro generation of NK cells from bone marrow cultures. Additional proliferation studies demonstrated that the up-regulation of c-myc protooncogene was associated with an increased uptake of thymidine. These data indicate that the TNF-alpha-induced increase of IL-2-dependent NK cell generation from bone marrow precursors was associated with an augmented proliferation and an up-regulation of mRNA expression for IL-2 receptor and c-myc protooncogene.

Animals↗