1,25-dihydroxyvitamin D-3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes

Astrocytes play a pivotal role in CNS detoxification pathways, where glutat hione (GSH) is involved in the elimination of oxygen and nitrogen reactive species such as nitric oxide. We have previously demonstrated that the spec ific activity of gamma-glutamyl transpeptidase (gamma-GT), an enzyme of cen tral 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 in vestigate, in primary cultures of newborn rat astrocytes, the effects of th is hormone on gamma-GT synthesis and on GSH and nitrite levels after lipopo lysaccharide (LPS) treatment. This study demonstrates that both gamma-GT ge ne expression and specific activity, induced by LPS, are potentiated by 1,2 5-D-3. In contrast, 1,25-D-3 does not regulate the expression of other enzy mes involved in astrocyte detoxification processes, such as superoxide dism utase or GSH peroxidase. In parallel, 1,25-D, enhanced intracellular GSH po ols and significantly reduced nitrite production induced by LPS. Taken toge ther, these results suggest that gamma-GT, GSH, and 1,25-D-3 play a fundame ntal role in astrocyte detoxification pathways.