Akademik Veri Yönetim Sistemi
CHEMICO-BIOLOGICAL INTERACTIONS, cilt.177, sa.1, ss.65-70, 2009 (SCI-Expanded)
Pregnenolone (P), the main precursor of the steroids, and its sulfate ester, pregnenolone sulfate (PS), are the major neurosteroids produced in the neural tissue. Many neuroendocrinological studies stressed the neuroprotective role of neurosteroids although it has been suggested that the inhibition of P and PS synthesis can delay neuronal cell death. The potential roles of P and PS in vital neuronal functions and in amyloid beta peptide (A beta) toxicity are not clearly identified. This work aims to investigate the effects of P and PS on cell viability and A beta peptide toxicity in a concentration and exposure time-dependent manner in rat PC-12 cells. The cells were treated with 20 mu M A beta peptide 25-35 and variable concentrations of P and PS ranging from 0.5 mu M to 100 mu W. To examine the effects of steroid treatment on A beta peptide toxicity. 0.5 mu M (low) and 50 mu M (high) neurosteroids were used. The cell viability and lactate dehydrogenase release of cells were evaluated after 24, 48 and 72h. Morphological changes of cells were also examined. The treatment with higher than 1 mu M concentrations of P and PS significantly decreased the cell viability comparing to untreated cells. At lower concentrations, P and PS had no toxic actions until 72h. The A beta treatment resulted in a significant decrease in cell viability comparing to untreated cells. P showed a dose-dependent protective effect against A beta peptide in PC-12 cells. But its sulfate ester did not have the same effect on A beta peptide toxicity, even it significantly decreased cell viability in A beta-treated cells. Consequently, the discrepant effects of P and PS on A beta peptide toxicity may provide insight on the pathogenesis of Alzheimer's disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved.