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Biomedical subjects

F Battaini

Publications and source records attributed to F Battaini.

86 records · Page 5Linked to original sources
PubMedDate not supplied

Regulation of phorbol ester binding and protein kinase C activity in aged rat brain.

Protein kinase C (PKC) function was analyzed in aged male Sprague-Dawley rat brain using two different approaches: the binding of [3H]-phorbol-12,13-dibutyrate and the in vitro phosphorylation of histone H1. In cortex the binding was decreased while in cerebellum no age-related modifications were observed. In hippocampus the binding capacity was increased in old animals and the affinity decreased. The kinase activity in both soluble and particulate fractions was decreased in cortex, increased in hippocampus and unmodified in cerebellum. The area selective, age-dependent modifications in neuronal PKC may sustain short- and long-term regional changes of neuronal excitability.

Age Factors↗
PubMedDate not supplied

Protein kinase C activity, translocation, and conventional isoforms in aging rat brain.

Protein kinase C was studied in various brain areas in aging Wistar rats. Histone-directed kinase activity from the cortex, hippocampus and cerebellum did not change with aging. Using purified protein B-50 as a substrate, between 3 and 8 months a decrease in in vitro phosphorylation was detected in the membrane fraction of the cortex but after this age values remained stable. In hippocampal membranes, B-50 phosphorylation was increased in aged rats. PKC translocation was impaired in aged rats in both the cortex and the hippocampus. PKC alpha and beta mRNA decreased in the cortex between 3 and 8 months with no further decline in aged animals. Hippocampal mRNA for calcium-dependent PKC isoforms was not modified during aging, as assessed by Northern and in situ hybridization. Western blot analysis revealed a change in PKC gamma protein only, which was increased in hippocampal membranes from aged rats. The data indicate that the key PKC function that is impaired in aged rats is enzyme translocation irrespective of the brain area investigated.

Aging↗
PubMedDate not supplied

Inositol 1,4,5-trisphosphate receptor and ryanodine receptor in the aging brain of Wistar rats.

Intracellular Ca2+ release channels are key players in the regulation of Ca2+ homeostasis. In the present study, we investigated the age-related changes of inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ release channel and ryanodine receptor/Ca2+ release channel in microsomes derived from either cerebellum or cerebrum cortex from male Wistar rats. A significant reduction (about 50%) in density of IP3 receptor/Ca2+ release channels was observed in cerebrum cortex, only, in 8- and 28-month old rats, whereas density and Kd of ryanodine binding sites were unaffected in both cerebellum and cerebrum microsomes. These findings, along with impairment of Ca(2+)-dependent protein kinase C phosphorylation of endogeneous substrates, point to coordinate, quantitative alterations of both targets of phosphoinositide metabolism, i.e., PKC and IP3 receptor, in the cerebrum cortex at least. The relevance of the present findings is discussed in relation to reported changes of neuronal Ca2+ homeostasis during aging.

Aging↗
PubMedDate not supplied

Calcium responses in human fibroblasts: a diagnostic molecular profile for Alzheimer's disease.

We have previously identified alterations of K+ channel function, IP3-mediated calcium release, and Cp20 (a memory-associated GTP binding protein) in fibroblasts from AD patients vs. controls. In the present study we introduce a scoring system based on these response alterations that integrates two or more alterations (and their degree) in AD vs. control fibroblasts. This scoring system generates an index that distinguishes AD patients from controls with both high specificity and sensitivity. We also show that low doses of bradykinin elicit intracellular calcium release almost exclusively in AD cell lines in an all or none fashion that provide a clear measurement of enhanced IP3-mediated function in AD vs. controls.

Aged↗
PubMedDate not supplied

Chronic alcohol intake modifies phorbol ester binding in selected rat brain areas.

3H-Phorbol 12,13 dibutyrate binding to rat brain was modified by chronic ethanol treatment. Among the areas examined hippocampus and cortex showed a decrease in Bmax values of 32 and 24% respectively. No significant effect was observed in hypothalamus and cerebellum. In vitro ethanol did not modify the binding in all the areas except at molar concentrations. In hippocampus and cortex the direct measurement of protein kinase C activity indicated that the decrease in phorbol ester binding was accompanied with a concomitant decrease in kinase activity. The results indicate that chronic ethanol treatment leads to an inhibition of brain protein kinase C function.

Animals↗
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Neuronal differentiation modifies the effect of ethanol exposure on voltage-dependent calcium channels in NG 108-15 cells.

The effect of prolonged (72 h) ethanol (200 mM) exposure on the labeling of L-type (using tritiated PN 200-110) and N-type (using iodinated omega-conotoxin) voltage-dependent calcium channels was investigated in cultured NG 108-15 cells. In undifferentiated cells ethanol produced an 80% increase in PN 200-110 Bmax and no changes in omega-conotoxin binding. Differentiation had a profound effect on the response of cells to ethanol, which in differentiated neuron-like cells decreased omega-conotoxin binding (-53.5%) leaving PN 200-110 labeling of L-type channels unaffected. The effect was time dependent and reversible upon ethanol withdrawal. The decreased omega-conotoxin binding was accompanied by a reduced ability of omega-conotoxin to inhibit K+ -stimulated calcium uptake. The results demonstrate that in cultured NG 108-15 cells ethanol differentially affects DHP and omega-conotoxin-sensitive, voltage-dependent calcium channels and that the effect is also modulated by differentiation of the cell to a neuronal phenotype.

Animals↗
PubMedDate not supplied

Increased natural killer cell cytotoxicity in Alzheimer's disease may involve protein kinase C dysregulation.

Increased cytokine-mediated cytotoxic natural killer (NK) cell activity has recently been demonstrated in patients with senile dementia of the Alzheimer's type (SDAT). In the present study, we evaluated whether protein-kinase C (PKC), a main regulatory enzyme involved in the mechanism of exocytosis by NK cells, has a role in the cytotoxic response of NK cells (during IL-2 and IFN-beta exposure) from SDAT patients. Our data demonstrate the presence of an increased cytotoxic response by NK cells to IL-2 (mean increase +102%) and IFN-beta (mean increase +132%) in SDAT patients in comparison with healthy elderly subjects (+75% and +88% for IL-2 and IFN-beta, respectively). A smaller suppression of NK cytotoxicity after cortisol was also observed in SDAT (mean decrease -24%) than in the control group (-44%). The NK cell activity of SDAT patients was inversely correlated with the cognitive status as evaluated by the analysis of MMSE (Mini Mental State Examination) score. A comparison of young and elderly healthy subjects revealed no variations in NK cell activity. A physiological decrease in cytosolic PKC activity was demonstrated in healthy old subjects after IL-2 and IFN-beta incubation, but not in SDAT patients, while no variations in kinase activity were observed after cortisol incubation. The decreased activity with cytokines was associated with reduced levels of PKC alpha and betaII isoforms. An alteration in cytokine-mediated NK cell activity associated with PKC dysregulation is therefore suggested to occur in patients with SDAT. These changes may indicate the existence of an immunological component to the pathogenesis and progression of the disease.

Adult↗
PubMedDate not supplied

STAT signalling in the mature and aging brain.

Activation of the Janus kinases (JAK) and signal transducers and activator of transcription (STAT) proteins in response to specific cytokines and growth factors has been investigated primarily in cells of non-neuronal origin. More recently, the JAKs and the STATs have also been found to be active in the developing and mature brain, providing evidence for important roles played by these molecules in the control of neuronal proliferation, survival and differentiation. Nothing, however, is known about their occurrence and role(s) in the aged brain. We, therefore, investigated the presence of Stat3 and Stat1 in aged-rat brain, and have found that the Stat3 protein was markedly down regulated with respect to adult tissue, while Stat1 remained invariant. We also investigated the potential role of some growth factors in the activation of the JAK/STAT in mature neurons, exposing primary neuronal cells to ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Besides CNTF, which is known to recruit Stat3, we found that Stat3 was also tyrosine phosphorylated by bFGF. These data are indicative of an important role of Stat3 and Stat1 in regulating the physiological status of mature neurons.

Aging↗
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Chronic low doses of ethanol affect brain protein kinase C and ultrasonic calls in rats.

Few studies have investigated neurobehavioral and neurochemical consequences of chronic consumption of low doses of ethanol. The present study shows that in rats exposure to 3% ethanol (v/v in drinking water) for 2 months decreased both calcium-dependent and -independent protein kinase C (PKC) activities in the cortex and in the hippocampus. This treatment also reduced ultrasonic calls (UCs), an index of emotional and motivational states of the animal. In addition, at cortical level of ethanol-treated rats, we observed a correlation between calcium-dependent activities and UCs. These results suggest that nonaddicting doses of ethanol affect brain PKC activities and that this enzyme may be involved in the ethanol modulation of emotional and motivational behaviors.

Animals↗
PubMedDate not supplied

Time-related asymmetric changes of brain microvessel beta-adrenergic receptors in the two hemispheres after carotid occlusion.

The effect of short term and long term ischemia induced by right carotid occlusion was studied on beta-adrenergic receptor function in rat cerebral microvessels. The results show a different time-dependent responsiveness of the two hemispheres to ischemia, with a pronounced and more persistent decrease in the number of capillary beta-receptors in the left side of the brain. The data suggest the existence of asymmetries in the control of brain microvasculature which may mediate the different time-course of beta-receptor changes in response to ischemia.

Animals↗
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Antibody response after vaccination with antigen-pulsed dendritic cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiating immune responses to antigens. It is also well documented that cancer patients often experience anergy against tumor antigens. In this study we selected the best protocol for inducing the production of antibodies against the HER2 oncoprotein using DCs to overcome anergy. Murine DCs were pulsed in vitro, using different protocols, with recombinant HER2 fused to a human Fc (in order to improve DC antigen uptake) and were used to vaccinate mice. The obtained results indicate that antigen-pulsed DCs can induce an antibody response and that adding CpG after antigen pulsing greatly increases anti-HER2 antibody production.

Animals↗
PubMedDate not supplied

Plasma prolactin concentrations in lead exposed workers.

Plasma Prolactin (Prl) Zinc protoporphyrin (Zpp) and blood lead concentrations (PbB) were measured in 76 exposed male workers. All of them were employed in small (not more than 30 persons) pewter factories and were randomly selected from those regularly controlled by the National Health Service, Occupational Health Unit of Brescia (USSL 41). Although all plasma Prl values were within the normal range, the mean value of the subgroup having Zpp and PbB higher than 40 micrograms/dl was significantly higher (+47%) than that observed in the group of workers having Zpp and PbB less than 40 micrograms/dl. The data indicate the possibility of a lead-induced Prl secretion dysfunction, probably mediated by a decrease in dopaminergic inhibitory control.

Adult↗