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C Bellone

Publications and source records attributed to C Bellone.

8 recordsLinked to original sources
PubMed2002

Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats.

In animal models of diabetes mellitus, such as the streptozotocin-diabetic rat (STZ-rat), spatial learning impairments develop in parallel with a reduced expression of long-term potentiation (LTP) and enhanced expression of long-term depression (LTD) in the hippocampus. This study examined the time course of the effects of STZ-diabetes and insulin treatment on the hippocampal post-synaptic glutamate N-methyl-D-aspartate (NMDA) receptor complex and other key proteins regulating hippocampal synaptic transmission in the post-synaptic density (PSD) fraction. In addition, the functional properties of the NMDA-receptor complex were examined. One month of STZ-diabetes did not affect the NMDA receptor complex. In contrast, 4 months after induction of diabetes NR2B subunit immunoreactivity, CaMKII and Tyr-dependent phosphorylation of the NR2A/B subunits of the NMDA receptor were reduced and alphaCaMKII autophosphorylation and its association to the NMDA receptor complex were impaired in STZ-rats compared with age-matched controls. Likewise, NMDA currents in hippocampal pyramidal neurones measured by intracellular recording were reduced in STZ-rats. Insulin treatment prevented the reduction in kinase activities, NR2B expression levels, CaMKII-NMDA receptor association and NMDA currents. These findings strengthen the hypothesis that altered post-synaptic glutamatergic transmission is related to deficits in learning and plasticity in this animal model.

Animals↗
PubMed2001

Cyclin-dependent kinase 2 nucleocytoplasmic translocation is regulated by extracellular regulated kinase.

Activation of cyclin-dependent kinase 2 (CDK2)-cyclin E in the late G(1) phase of the cell cycle is important for transit into S phase. In Chinese hamster embryonic fibroblasts (IIC9) phosphatidylinositol 3-kinase and ERK regulate alpha-thrombin-induced G(1) transit by their effects on cyclin D1 protein accumulation (Phillips-Mason, P. J., Raben, D. M., and Baldassare, J. J. (2000) J. Biol. Chem. 275, 18046-18053). Here, we show that ERK also affects CDK2-cyclin E activation by regulating the subcellular localization of CDK2. Ectopic expression of cyclin E rescues the inhibition of alpha-thrombin-induced activation of CDK2-cyclin E and transit into S phase brought about by treatment of IIC9 cells with LY29004, a selective inhibitor of mitogen stimulation of phosphatidylinositol 3-kinase activity. However, cyclin E expression is ineffectual in rescuing these effects when ERK activation is blocked by treatment with PD98059, a selective inhibitor of MEK activation of ERK. Investigation into the mechanistic reasons for this difference found the following. 1) Although treatment with LY29004 inhibits alpha-thrombin-stimulated nuclear localization, ectopic expression of cyclin E rescues CDK2 translocation. 2) In contrast to treatment with LY29004, ectopic expression of cyclin E fails to restore alpha-thrombin-stimulated nuclear CDK2 translocation in IIC9 cells treated with PD98059. 3) CDK2-cyclin E complexes are not affected by treatment with either inhibitor. These data indicate that, in addition to its effects on cyclin D1 expression, ERK activity is an important controller of the translocation of CDK2 into the nucleus where it is activated.

Animals↗
PubMed2000

Protein kinase C activation modulates alpha-calmodulin kinase II binding to NR2A subunit of N-methyl-D-aspartate receptor complex.

The N-methyl-d-aspartate (NMDA) receptor subunits NR2 possess extended intracellular C-terminal domains by which they can directly interact with a large number of postsynaptic density (PSD) proteins involved in synaptic clustering and signaling. We have previously shown that PSD-associated alpha-calmodulin kinase II (alphaCaMKII) binds with high affinity to the C-terminal domain of the NR2A subunit. Here, we show that residues 1412-1419 of the cytosolic tail of NR2A are critical for alphaCaMKII binding, and we identify, by site directed mutagenesis, PKC-dependent phosphorylation of NR2A(Ser(1416)) as a key mechanism in inhibiting alphaCaMKII-binding and promoting dissociation of alphaCaMKII.NR2A complex. In addition, we show that stimulation of PKC activity in hippocampal slices either with phorbol esters or with the mGluRs specific agonist trans-1-amino-1,3- cyclopentanedicarboxylic acid (t-ACPD) decreases alphaCaMKII binding to NMDA receptor complex. Thus, our data provide clues on understanding the molecular basis of a direct cross-talk between alphaCaMKII and PKC pathways in the postsynaptic compartment.

Animals↗
PubMed2000

Dry adsorbed emulsion: 1. Characterization of an intricate physicochemical structure.

A recent solid pharmaceutical form called "Dry Adsorbed Emulsion" (DAE) was characterized in morphological and structural fields. A DAE is an intricate system initiated by a water-in-oil emulsion including the active drug (i.e., theophylline). Each emulsion phase is adsorbed on pulverulent adsorbents with a suitable polarity (silica) to obtain a free-flowing powder with nonporous particles of size from 125 to 710 microm, with small specific surface area and a spherical shape. Different methods, such as scanning electron microscopy combined with chemical microanalysis, dying tests, and electron spin resonance studies, allow the formulator to follow the behavior of DAE aqueous and oily phases during the manufacturing process and then to set up a structural model for DAE particles. These DAE particles appear to be made up of a random pack of hydrophilic and hydrophobic particles, containing a liquid phase adsorbed on silica by weak bonds.

Adsorption↗
PubMed1990

[Growth factors in human tooth development].

Our research concerns the immunohistochemical localization of EGF and IGF-I receptors in the tooth germ, using monoclonal antibodies. The results show that in the early phases of human tooth development EGF and IGF-I receptors are present. At bud stage both receptors are localized at dental laminae level, in some epithelial cells of the tooth bud and in some mesenchymal cells. At cap stage the receptors are present in the outer and inner enamel epithelium, and in some cells of stellate reticulum. As far as concerns the mesenchymal cells, some cells of dental papilla in contact with enamel organ, are intensely positive. The immunopositivity is present also in some mesenchymal cells at follicular level. At late cap stage and at early bell stage receptors are not present at inner enamel epithelium level but they can be detectable in the mesenchyma of dental papilla and in some cells of the follicle. On the basis of these results it may be hypothesized that EGF and IGF-I can act as growth factors in the modulation of cellular proliferation and differentiation during the human tooth morphogenesis. Moreover, it is possible that these substances can play a role in the mesenchymal-epithelial interaction in the developing human tooth.

Cell Differentiation↗
PubMedDate not supplied

Characterization and localization of epidermal growth factor receptors in human developing tooth.

In this study the characterization and localization of Epidermal Growth Factor (EGF) receptor in human jaws, from fetuses ranging in age from 9 to 12 weeks is reported for the first time. Binding of [125I]-EGF to membranes obtained from three separate pools of fetal jaws was specific and time- and temperature-dependent. Analysis of the binding data revealed the presence of a single class of binding site with high affinity (Kd, 9.2 x 10(-10) mol/L) and mean binding capacity of 128 fmoles/mg protein. Immunohistochemical study demonstrated the presence of EGF receptors in the early developmental stages of human tooth. In the bud stage, the positivity was localized in the epithelial cells. In the cap stage, EGF receptors was present in the outer and inner enamel cells, in some cells of the stellate reticulum and in the mesenchymal papilla and follicle cells. In the bell stage, positivity for EGF receptors was present in the outer enamel epithelium, in some cells of the stellate reticulum and in the mesenchymal cells of the follicle and papilla. The presence of EGF receptors in the proliferative stages in both epithelial and mesenchymal cells suggests that EGF is involved in the early developmental stages of the human tooth germ.

Dental Enamel↗