A novel mechanism for pergolide-induced neuroprotection: inhibition of NF-kappaB nuclear translocation.

We previously demonstrated that the dopaminergic agonist pergolide, independently from its DA agonist activity, can exert neuroprotective effects against cell death induced in SH-SY5Y neural cells by H(2)O(2) treatment. Since oxidative stress in SH-SY5Y neural cells is known to activate the NF-kappaB pathway we tested the hypothesis that pergolide may interfere with NF-kappaB activity. Based on Western blot analysis and immunocytochemistry, pergolide was found to prevent H(2)O(2)-induced apoptosis by inhibiting NF-kappaB nuclear translocation and activation of p53 signalling pathway. Similarly, the cell-permeable SN50 peptide, which is known to block NF-kappaB nuclear translocation, prevented both H(2)O(2)-induced p53 expression and apoptosis. The mechanism of action of pergolide responsible for neuroprotection differed from that of antioxidants. In fact, Vitamin E, contrary to pergolide and SN50, rescued neuronal cells from H(2)O(2)-induced apoptosis acting upstream NF-kappaB activation, as demonstrated by the prevention of H(2)O(2)-induced IkappaB degradation. These data suggest a novel site of action of pergolide that may account for additional pharmacological properties of this drug.

Neutralization of TRAIL death pathway protects human neuronal cell line from beta-amyloid toxicity.

Here we report that a novel member of the TNF-alpha family, TNF-related apoptosis-inducing ligand (TRAIL), contributes substantially to amyloid-induced neurotoxicity in human SH-SY5Y neuronal cell line. Involvement of TRAIL in the amyloid-induced cell death is supported by cDNA array, Northern blot, and Western blot data, demonstrating increased TRAIL expression after treatment of the cells with a neurotoxic fragment of amyloid protein (betaAP). TRAIL was also found to be released in the culture media after betaAP treatment with a time-course overlapping to contents of the intracellular protein. Contribution of TRAIL to betaAP neurotoxicity is demonstrated by data showing that TRAIL-neutralizing monoclonal antibody protects neuronal SH-SY5Y cells from betaAP neurotoxicity. Moreover, exposure of neuronal SH-SY5Y cells to TRAIL leads to cell death, indicating that this substance per se is endowed with neurotoxic properties. We also found that, similarly to betaAP and TRAIL, activation of the death-domain adaptor protein FADD results in neuronal cell death. Lack of FADD function, by overexpression of its dominant negative, rescued cells from either TRAIL- or betaAP-induced neurotoxicity, supporting the hypothesis that these three molecules share common intracellular pathways. Finally, we found that betaAP strongly activated caspase-8, and the cell-permeable, selective caspase-8 inhibitor z-IETD-FMK prevents both betaAP- and TRAIL-induced neurotoxicity. In view of TRAIL's potency in inducing neuronal death, and its role as mediator of betaAP, it is plausible to hypothesize that TRAIL can be regarded as a molecule that provides substantial contribution to betaAP-dependent cell death, which takes part in the progression of the neurodegenerative process and related chronic inflammatory response.

[Protein content of latex gloves used in hospitals]. / Proteine estraibili del latice in guanti di impiego ospedaliero.

In this study the total protein content and the latex allergenic protein content in different types of medical gloves commonly used in our hospital were evaluated. The correlation between these two parameters and the correctness of the data provided by the glove manufacturers have been also verified. The main purpose of this study was to acquire information useful for preventing latex allergy in our hospital personnel. 29 different types of medical gloves were examined. The total protein contents were evaluated with Lowry modified method and the allergenic latex protein contents were evaluated with RAST-inhibition assay, both on glove samples and glove extracts. The correlation between inhibition percentages found in glove samples and in glove extracts and the correlation between total protein content and inhibition percentages determined in samples of the same gloves was verified. The highest concentrations of total proteins and allergenic latex proteins were found in examination powdered latex gloves and in surgical powdered latex gloves. A good correlation was observed between the total protein content and the inhibition percentages determined in samples of the same gloves, and between inhibition percentages found in glove samples and glove extracts. A significant amount of latex proteins was found in some brands of nitryl gloves. The clear association between the total protein levels and the allergenic latex protein levels suggests that the gloves with highest total protein content have the greatest allergenic potential. We believe that the total protein content is relevant from a preventive point of view for a proper gloves selection in the workplaces. Therefore, manufacturing companies should provide package inserts including at least the total protein contents and possibly allergenic latex protein levels, with specific measurement methods. Since the highest total protein and allergenic latex protein contents were found in latex powdered gloves, powder-free gloves must be of first choice. RAST-inhibition assays directly on glove samples instead of glove extract seems to be a good reliable and faster alternative for the evaluation of the allergenic potential of latex gloves. For latex allergic subjects it is necessary to pay attention in choosing nitryl gloves, especially as an alternative to natural rubber gloves since some brands may contain significant amounts of allergenic latex proteins.