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M Salmona

Publications and source records attributed to M Salmona.

206 records · Page 12Linked to original sources
PubMedDate not supplied

Aging and food restriction: effect on lipids of cerebral cortex.

In experimental animals dietary restriction reduces the body weight increase due to aging, increases longevity and delays the onset of age-related physiological deterioration, including age-related changes in serum lipids. Little is known about the influence of food restriction on brain lipids, whose concentration and composition have been shown to change with age. We studied whether some biochemical and biophysical parameters of rat brain membranes, known to be modified with age, were affected by a diet low in calories, in which 50% of lipids and 35% of carbohydrates have been replaced by fibers. The diet was started at weaning and maintained throughout the animal's entire life span. Animals fed the low calorie diet survived longer and gained less body weight than standard diet fed rats. Age-related increases in microviscosity, cholesterol/phospholipid and sphingomyelin/phosphatidylcholine ratios were reduced or restored to the levels of young animals in cortex membranes of 32 old rats fed the low calorie diet, while the age-related increase in mono- to polyunsaturated fatty acid ratios in phospholipids was further raised. In conclusion we have shown that a diet low in calories and high in fibers affects lipid composition in the rat brain, in a direction opposite to that normally believed to reduce age-related deterioration of brain functions.

Aging↗
PubMedDate not supplied

Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106-126.

Prion encephalopathies include fatal diseases of the central nervous system of men and animals characterized by nerve cell loss, glial proliferation and deposition of amyloid fibrils into the brain. During these diseases a cellular glycoprotein (the prion protein, PrP(C)) is converted, through a not yet completely clear mechanism, in an altered isoform (the prion scrapie, PrP(Sc)) that accumulates within the brain tissue by virtue of its resistance to the intracellular catabolism. PrP(Sc) is believed to be responsible for the neuronal loss that is observed in the prion disease. The PrP 106-126, a synthetic peptide that has been obtained from the amyloidogenic portion of the prion protein, represents a suitable model for studying the pathogenic role of the PrP(Sc), retaining, in vitro, some characteristics of the entire protein, such as the capability to aggregate in fibrils, and the neurotoxicity. In this work we present the results we have recently obtained regarding the action of the PrP 106-126 in different cellular models. We report that the PrP 106-126 induces proliferation of cortical astrocytes, as well as degeneration of primary cultures of cortical neurons or of neuroectodermal stable cell lines (GH(3) cells). In particular, these two opposite effects are mediated by the same attitude of the peptide to interact with the L-type calcium channels: in the astrocytes, the activity of these channels seems to be activated by PrP 106-126, while, in the cortical neurons and in the GH(3) cells, the same treatment causes a blockade of these channels causing a toxic effect.

Amino Acid Sequence↗
PubMedDate not supplied

Fluorescence polarization changes with gestational age in amniotic fluid of rabbit and guinea pig.

The variation of amniotic fluid microviscosity with gestational age was measured in rat, rabbit, and guinea pig. In rat, the changes followed the same pattern as known for women, microviscosity being high during early and mid-gestation and markedly lowering 12 h before delivery. Surprisingly, an opposite trend was observed in rabbit and guinea pig amniotic fluid. Moreover, the lecithin to sphingomyelin ratio markedly rose in late gestation in all species considered. Qualitative and quantitative analysis of lipids and phospholipids were performed in woman and rabbit amniotic fluids at early and late gestational ages. Among all the parameters measured, the most important differences that can influence the amniotic fluid microviscosity are the presence of very high levels of lysophosphatidylcholine both in early and late gestation in rabbit (much higher than in woman) and the cholesterol to total phospholipid ratio which decreased with gestational age in woman but remained stable in rabbit. The Arrhenius plot of the logarithm of microviscosity against the reciprocal of absolute temperature of mature and immature amniotic fluids from woman and rabbit was also determined. The temperature profiles confirmed the differences in lipid profile between woman and rabbit in early and late gestation which could be quantified on a physicochemical basis by determining the activation energy (delta E) at 25 degrees and 37 degrees C for each curve. This confirmed the opposite patterns in woman and rabbit and showed that amniotic fluid from the immature rabbit was the most fluid.

Amniotic Fluid↗
PubMedDate not supplied

Endotoxin regulates the maturation of sterol regulatory element binding protein-1 through the induction of cytokines.

Endotoxin (LPS), by raising the levels of cytokines, markedly influences lipid metabolism. To clarify the molecular mechanism of this effect, we examined the action of endotoxin in vitro and in vivo on the regulation of sterol regulatory element binding protein-1 (SREBP-1). In HepG2 cells stimulated with LPS, a dose-dependent increase in the level of the mature form of SREBP-1 was observed. For in vivo studies, endotoxin was administered intraperitoneally to CD1 mice fed with a standard or a cholesterol-enriched diet to increase the basal levels of circulating and liver cholesterol. Endotoxin raised cholesterol levels and stimulated the maturation of hepatic SREBP-1 in both normal and cholesterol-fed mice, indicating that the lipogenic effect of LPS was independent of endogenous sterol levels. To assess whether the lipogenic effect of endotoxin was linked to cytokine production, we administered LPS to C57Bl/6J endotoxin-sensitive and to C3H/HeJ endotoxin-resistant mice, which do not produce tumor necrosis factor in response to LPS. Significant induction of cholesterol levels and SREBP-1 activation was observed only in C57Bl/6J mice, indicating that cytokine production is crucial for the regulation of SREBP-1, and that the transcriptional activation of cholesterol biosynthesis may be part of the acute-phase response.

Animals↗
PubMedDate not supplied

Possible relevance of N-trifluoroacetyladriamycin (AD 41) in the antitumoral activity of N-trifluoroacetyladriamycin-14-valerate (AD 32) in tumor-bearing mice. I. Pharmacokinetic evidence.

N-Trifluoroacetyladriamycin-14-valerate (AD 32) is an analog of doxorubicin whose chemico-physical characteristics are nontypical compared to the parent compound. Its most interesting feature is the lack of capacity to intercalate with DNA; thus, its mechanism of action as an antitumoral drug is still unknown. The N-trifluoroacetyl bond on the glycoside moiety is very stable and does not easily undergo enzymatic hydrolysis. Conversely, the valerate ester is split very rapidly by tissue and blood hydrolases. In this paper we present a kinetic study on AD 32, and we additionally follow the formation and disappearance of its metabolite, N-trifluoroacetyladriamycin (AD 41). Peak levels, areas under the curve, and beta-half-lives of AD 32 and AD 41 after an iv injection of 80 mg/kg of AD 32 to Lewis lung carcinoma-bearing mice are presented. The results indicated very rapid disappearance of AD 32 from blood and tissues, whereas AD 42 persisted for much longer. Moreover, all of the tissues taken into consideration were able to hydrolyze AD 32 to AD 41, suggesting that this compound plays an important role in the antitumoral activity of AD 32.

Animals↗
PubMedDate not supplied

Protein kinase C is not involved in cholesterol-induced resistance to synthetic ether lipids.

The possible role of protein kinase C in cholesterol-induced resistance to ether lipids was investigated. The enrichment of HL60 cells in cholesterol (CHOL) (HL60-CHOL) resulted in a significant increase in the ID50 values for 1-octadecyl-2-methyl-rac-glycero- 3-phosphocholine (ET-18-OMe) (3.75 +/- 0.7 microM and 6.69 +/- 0.5 microM for HL60 and HL60-CHOL, respectively). In the same conditions, HL60 and HL60-CHOL cells showed comparable levels of both cytosolic and membrane-associated protein kinase C activity. Phorbol ester (PMA) stimulation induced protein kinase C to translocate from the cytosol to the plasma membrane in both cell types and with similar kinetics (272 +/- 32% and 299 +/- 41% increase in HL60 and HL60-CHOL, respectively after 100 ng/ml PMA for 10 min). Pretreatment of the two cell types with 50 microM ET-18-OMe resulted in comparable levels of PKC inhibition after phorbol ester stimulation. These results suggested that alterations in plasma membrane lipid composition induced by CHOL do not result in major changes in protein kinase C activity. Thus, protein kinase C does not appear to be involved in cholesterol-induced resistant phenotype in HL60 cells.

Cholesterol↗