Astrocytes play a pivotal role in CNS detoxification pathways, where glutathione (GSH) is involved in the elimination of oxygen and nitrogen reactive species such as nitric oxide. We have previously demonstrated that the specific activity of ␥-glutamyl transpeptidase (␥-GT), an enzyme of central significance in GSH metabolism, is regulated in vivo in astrocytes by 1,25-dihydroxyvitamin D 3 (1,25-D 3 ). The aim of the present work was to investigate, in primary cultures of newborn rat astrocytes, the effects of this hormone on ␥-GT synthesis and on GSH and nitrite levels after lipopolysaccharide (LPS) treatment. This study demonstrates that both ␥-GT gene expression and specific activity, induced by LPS, are potentiated by 1,25-D 3 . In contrast, 1,25-D 3 does not regulate the expression of other enzymes involved in astrocyte detoxification processes, such as superoxide dismutase or GSH peroxidase. In parallel, 1,25-D 3 enhanced intracellular GSH pools and significantly reduced nitrite production induced by LPS. Taken together, these results suggest that ␥-GT, GSH, and 1,25-D 3 play a fundamental role in astrocyte detoxification pathways.
The strategy chosen for cloning potential vaccine antigens of Toxoplasma gondii was based on the hypothesis that the definitive protection observed in natural infection is due to the presence of encysted bradyzoite forms in host tissues throughout life. The antigens released by the bradyzoites would maintain an immune response against the invading tachyzoites. This led us to identify in tachyzoite in vitro translation products a polypeptide of 24 kDa that is an excreted-secreted antigen (ESA) and is cross-reactive with bradyzoites. In addition, the detection of anti-P24 IgG antibodies is correlated with the chronic infection in man. The gene encoding P24 has been isolated, sequenced, and expressed in Escherichia coli and eukaryotic cells. The recombinant proteins were immunogenic in mice, producing anti-native P23 antibodies. Immunocytochemical analysis located the native antigen in the dense granules of both tachyzoite and bradyzoite forms and showed that it is secreted within host-cell-modified phagosome. Moreover 45Ca2+ labeling as well as regional homologies indicate that this protein has Ca2+-binding properties, suggesting its physiological importance in host-cell invasion. P23 is of diagnostic interest as a marker of chronic toxoplasmosis and is proposed as a vaccine component.
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