Search PubMed⌕ Search

Biomedical subjects

F Battaini

Publications and source records attributed to F Battaini.

At least 37 records · Page 2Linked to original sources
PubMed1994

Characterization and distribution of protein kinase C isoforms in human skin fibroblasts.

In the present study we have examined the distribution of several isoforms of protein kinase C, a lipid-regulated serine/threonine kinase essential for signal transduction and cell regulation, in cultured human skin fibroblasts. By Western blot analysis we have detected the presence of at least three of the known protein kinase C isoforms. The calcium-dependent protein kinase C alpha was primarily associated with the cytosolic fraction. Three non-calcium-dependent isoforms, protein kinases C epsilon, C delta, and C zeta, were also detected. Protein kinases C zeta and C delta were present primarily in the cytosol, while protein kinase C epsilon was associated primarily with the membrane fraction. Binding and activity studies were consistent with the pattern of expression and distribution defined by Western blot analysis. These results provide a useful frame of reference for the study of isoform-specific effects of protein kinase C in the regulation of cell growth and metabolism.

Adult↗
PubMed1993

PKC translocation in rat brain cortex is promoted in vivo and in vitro by alpha-glycerylphosphorylcholine, a cognition-enhancing drug.

Protein kinase C (PKC) activity was measured in soluble and particulate fractions of rat individual brain areas after treatment with alpha-glycerylphosphorylcholine (GPC), a cognition-enhancing drug which promotes acetylcholine synthesis and release. The drug induced both in vivo and in vitro PKC translocation. In vivo, an increase of particulate PKC activity was observed 1 hour following the acute oral administration of a behaviorally active dose (600 mg/kg); the effect was transient. In vitro, GPC promoted PKC translocation in cortical slices at concentrations as low as 50 nM; the concentration-response curve was bell shaped. The increased PKC activity may be related to the cortical effects of GPC.

Amphetamine↗
PubMed1993

Cognition stimulating drugs modulate protein kinase C activity in cerebral cortex and hippocampus of adult rats.

The in vivo and in vitro effect of oxiracetam, aniracetam and alpha-glycerylphosphorylcholine (alpha GPC) on protein kinase C (PKC) activity was studied in rat brain cortex and hippocampus. Administration of oxiracetam and alpha GPC in vivo elicited an early increase of particulate histone-directed PKC activity accompanied by a decrease of soluble activity and followed a few hours later by a down regulation of the enzyme. The effect was also observed in vitro when either oxiracetam or alpha GPC were administered at nanomolar concentrations to rat brain cortex slices. Aniracetam had no effect in the cortex but promoted PKC translocation both in vivo and in vitro in the hippocampus. In cortex slices the effect of oxiracetam was antagonized by the addition of AP-5, an NMDA receptor blocker, but not by CNQX and L-AP3, antagonists of AMPA and metabotropic glutamate receptors, respectively. Scopolamine also prevented the increase of particulate PKC elicited by oxiracetam in vitro. In the hippocampus the increase of particulate PKC activity was antagonized by AP-5, CNQX and L-AP3, indicating participation by both ionotropic and metabotropic glutamate receptors in the action of aniracetam. The data support the hypothesis that PKC activation may be a common mechanism amongst cognition stimulating drugs from different chemical classes.

Animals↗
PubMed1993

Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease patients.

We attempted to determine whether changes in protein kinase C (PKC) activity in Alzheimer's disease (AD) brains are also present in cultured skin fibroblasts from living patients. Biopsies collected from shoulder skin were transferred to culture plates with an appropriate growth medium, and histone-directed PKC activity as well as phorbol ester binding were individually determined in soluble and particulate fractions prepared from AD and non-AD fibroblast cell lines. Binding experiments indicated that PKC was unevenly distributed between cytosol (78%) and particulate (22%). The Bmax values for phorbol ester binding in soluble and particulate fractions were similar in AD and non-AD patients. Kd values in the cytosol were 94% higher in AD patients, indicating lower affinity of the enzyme for the ligand. Accordingly, the soluble PKC activity was 30% lower in AD patients. The data suggest that the changes in PKC phosphorylating activity represent a diffuse cellular defect in AD and are not confined to the brain. The alterations of the enzyme may participate in the disregulation in processing of beta-amyloid precursor protein in AD.

Aged↗
PubMed1993

Effect of ethanol exposure on voltage-dependent calcium channels in in vitro cellular models.

Chronic ethanol exposure alters calcium movements and the number of dihydropyridine (DHP) binding sites in the animal brain and in cultured neural cell lines. The present study investigates the effect of ethanol treatment on dihydropyridine- and omega-conotoxin (CgTx)- labelled calcium channels in undifferentiated and differentiated NG 108-15 cells. Following differentiation, the binding of [3H] -PN 200-110 increased by 48% while [125I]-CgTx binding increased by six fold. In accordance with data in the literature, undifferentiated cells exposed to ethanol (3 days) showed a large increase (70%) in DHP binding sites. In contrast, CgTx binding sites were unmodified by the treatment. Using differentiated cells, ethanol exposure induced a significant decrease (53%) in CgTx binding sites without altering those labelled by PN 200-110 (isradipine). These findings indicate that the effect of ethanol exposure on calcium channels may be dependent on the type of channel considered and on the status of the cells treated.

Animals↗
PubMed1992

Protein kinase C increase in rat brain cortical membranes may be promoted by cognition enhancing drugs.

Protein Kinase C (PKC) activity was measured in soluble and particulate fractions of rat individual brain cortices after in vivo treatment with two cognition enhancers: oxiracetam and alpha-glicerylphosphorylcholine. Both drugs induced an increase (+40-50%) of PKC particulate activity at 1 hr after the treatment. The effect was transient; at 5 hours PKC activity was lower than in controls. The dose response curve to oxiracetam was bell shaped, the increase of PKC being significant at 100 mg/kg. At higher doses the drug induced a decrease in enzyme activity. The increased PKC activity may be related to the cortical effects of these compounds.

Animals↗
PubMed1992

G protein modulation of omega-conotoxin binding sites in neuroblastoma x glioma NG 108-15 hybrid cells.

Electrophysiological evidence shows that voltage-dependent calcium channel (VDCC) activity can be regulated by a large number of neurotransmitters. In particular, guanine nucleotide binding regulatory protein (G protein)-mediated inhibitory modulation of the channel activity has been deduced from evidence that GTP analogues and purified G proteins are able to mimic this effect. The G proteins involved are pertussis toxin (PTx) sensitive. The purpose of the present study was to investigate, using biochemical techniques, whether G protein activation modulates the recognition site for omega-conotoxin GVIA (CgTx), a peptide neurotoxin that selectively labels a population of high-threshold VDCC. Undifferentiated and differentiated (1 mM dibutyryl cyclic AMP, 4 days) NG 108-15 cells were used. In both crude cellular extracts specific binding of 125I-CgTx was characterized. Differentiation induced a sixfold increase in the number of binding sites and doubled the KD value. The in vitro addition of guanylylimidodiphosphate (GMP-PNP; a nonhydrolyzable analogue of GTP) to extracts prepared from differentiated cells reduced the 125I-CgTx binding by 48%. This effect, observed in undifferentiated cells as well, was also caused by other triphosphate guanine nucleotides, such as GTP, but not by guanosine 5'-O-(2-thiodiphosphate) or adenine nucleotides. Treatment of the cells with PTx prevented the GMP-PNP effect. Moreover, the results obtained after preincubation with specific antisera raised against the alpha subunits of Gi1-2 and Go suggest that Go is the G protein responsible for the observed effect.

Animals↗
PubMed1991

The aging brain: protein phosphorylation as a target of changes in neuronal function.

There is evidence that senescence affects neurotransmission at different levels. In particular, this review summarizes the studies on age-dependent modifications in protein phosphorylation, which represents the final pathway in the action of transmitters and hormones at neuronal level. Cyclic AMP-dependent protein kinase and protein kinase C have been reported to be modified during aging in various cerebral areas; the changes may involve either enzyme activity or substrate availability. These findings can be related to the alterations in neurotransmitter function and synaptic efficiency observed in the senescent brain. The activity of the other types of protein kinases (tyrosine-, cGMP-, calcium/calmodulin-dependent) during aging needs to be explored. An emerging point is the role of protein phosphorylation in the transfer of membrane signals to the nucleus, for the activation or disactivation of specific genes responsible for long-term neuronal events. Along this view, alterations in protein kinase pathway during senescence would ultimately affect gene expression, resulting in long term modifications of cell function. The reviewed literature opens the perspective of restoring some of the deficits associated with senescence by modulating protein phosphorylation pathway.

Aging↗
PubMed1991

Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine.

The present study investigates the effect of the administration of alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced amnesia and on brain acetylcholine (ACh) levels and release in rats. The results indicate that alpha-GPC, when administered orally, reverses the amnesia caused by scopolamine in passive avoidance. The peak effect is observed using 600 mg/kg IG, 5 h before training. The effect of the drug is long lasting (up 30 h) in accordance with its pharmacokinetic characteristics. Since, alpha-GPC administered IG is cleaved within the gut mucosal cells to glycerophosphate and free choline, it is tempting to speculate that this drug acts by increasing the ACh precursor pool. This view is supported also by the observation that alpha-GPC partially counteracts the decrease of brain ACh levels elicited by scopolamine administration. The effect is observed in the hippocampus and cortex, but not in the striatum. Moreover, in ex vivo experiments, alpha-GPC is able to increase the amount of ACh released by rat hippocampus slices following potassium stimulation.

Acetylcholine↗
PubMed1991

Evaluation of beta-endorphin/beta-lipotropin immunoreactivity content in the CSF of patients affected by deafferentation pain syndromes.

Beta-endorphin/beta-lipotropin immunoreactivity (BE/BLPH-IR) content was evaluated in the CSF of patients suffering by deafferentation pain syndromes. BE/BLPH-IR CSF concentrations of these patients were compared with those obtained in a group of patients affected by low back pain and in a control group without pain problems. No statistically significant variation in BE/BLPH-IR levels were found between controls and subjects with different types of chronic pain.

Adult↗
PubMed1990

Calcium antagonists inhibit met-enkephalin immunoreactive material release: in vitro and ex vivo experiments.

Depolarizing stimuli increase the release of neurotransmitter met-enkephalin from rat striatal slices. Bay K8644, a calcium agonist, significantly enhances the submaximal release of this peptide. Several organic calcium antagonists, including nimodipine, nifedipine, nicardipine, gallopamil and flunarizine, are able to inhibit the potassium-evoked met-enkephalin release both in vitro and ex vivo. The data suggest that the release of this neuropeptide is modulated by calcium antagonist-sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Modulation of dihydropyridine-sensitive calcium channels: a role for G proteins.

The present study investigates the effect of G protein activation on dihydropyridine recognition sites in PC12 cell membranes. The addition of a stable analogue of GTP, GMP-PNP, increases the displacement of tritiated PN 200-110 produced by Bay K 8644 without modifying the one produced by nitrendipine. This effect is prevented by Pertussis toxin treatment. Functional studies based on the measurement of intracellular calcium concentrations by means of the fura 2 technique show that Pertussis toxin reduces the ability of Bay K8644 to potentiate the increase of cytosolic calcium elicited by 80 mM K+. The results support the hypothesis that a G protein may modulate the activity of voltage-dependent, dihydropyridine-sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Decrease in phorbol ester receptors in human brain tumors.

We have characterized the specific binding of [3H]-phorbol-12,13-dibutyrate in the white and gray matter of normal human brain and in cerebral tumors as an index of the availability of protein kinase C enzyme molecules. White matter has less than 50% phorbol-ester-binding capacity in comparison to gray matter. The binding is lower in tumors of glial origin when compared with normal white matter. Tumors of nonglial origin such as neurinoma and meningioma have a lower binding capacity than glial tumors. Metastatic tissues have the lowest binding capacity. The analysis of binding parameters in tumors and in the corresponding normal peritumoral tissues confirms the decreased binding capacity of neoplastic tissues in comparison to tissues not undergoing malignant transformation. These data suggest that brain glial tumors have a low availability of protein kinase C enzyme molecules and point to the potential involvement of this system in malignant transformation of human brain cells.

Adult↗
PubMed1988

Effect of chronic calcium antagonist treatment on dopamine recognition sites in rat striatum.

The effects of nimodipine and flunarizine administration (18 days 15 mg/kg/day p.o.) on striatal dopamine recognition sites in rats were investigated in vivo. In vitro flunarizine but not nimodipine displaces [3H]spiroperidol binding. After in vivo treatment both drugs induce a significant increase in the number of sulpiride displaceable spiroperidol binding sites (flunarizine, +114%, nimodipine +61%) concomitant with an increase in the dissociation constant. Binding parameters return toward control values after 1 week of suspension of the treatment. The results suggest that the repeated in vivo treatment with nimodipine and flunarizine may significantly interact with dopaminergic transmission leading to adaptive changes of the dopamine recognition sites.

Animals↗
PubMed1988

L-type calcium channels are modified in rat hippocampus by short-term experimental ischemia.

Increasing evidence suggests a role for calcium ions in the pathophysiology of ischemic brain damage. The major mechanism allowing calcium entry from the extracellular compartment is the opening of voltage-operated calcium channels. In this line, we have explored the hypothesis that the characteristics of central L-type voltage-dependent calcium channels, labeled by the dihydropyridine ligand 3H-PN 200-110, may be modified by experimental ischemia. The results show that short-term mild ischemia, produced in the rat by 1 h of right carotid ligation, induces an increase in the number of 3H-PN 200-110 binding sites in the hippocampus ipsilateral to the side of carotid occlusion, accompanied by an increase in the dissociation constant value, whereas no changes in the kinetic parameters of the binding were observed in the other areas examined, i.e., the cortex and the striatum. The changes in hippocampus are transient: 96 h after the occlusion, binding parameters return to the control range. The modifications of the binding characteristics in the hippocampus may be related to alterations of Ca2+ fluxes through L-type calcium channels.

Animals↗
PubMed1988

Reduced cAMP-dependent phosphorylation in striatum and nucleus accumbens of aged rats: evidence of an altered functioning of D1 dopaminoceptive neurons.

Cyclic AMP-dependent phosphorylation was measured in particulate and in cytosolic fractions of two brain dopaminergic areas, i.e., striatum and nucleus accumbens, of young (3 months) and old (24 months) rats. A reduced cAMP-stimulated 32P incorporation was observed in several protein bands in both brain areas in the aged group. In the soluble fraction the reduced phosphorylation of DARPP-32, which is specific for dopaminoceptive neurons bearing D-1 receptors, may be of particular relevance in the mechanisms of age-related changes in dopaminergic transmission.

Aging↗