H2S RELEASING ASPIRIN PROTECTS AMYLOID BETA INDUCED CELL TOXICITY IN BV-2 MICROGLIAL CELLS

beta-Amyloid (A beta) plaques are characteristic hallmarks of Alzheimer's disease. In the present study, we examined the neuroprotective effects of S-aspirin, a hydrogen sulfide (H2S)-releasing aspirin, on A beta-induced cell toxicity. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay showed that S-aspirin, but not aspirin, significantly increased cell viability in BV-2 microglial cells, indicating that S-aspirin may protect cells against injury via releasing H2S. S-aspirin at 2.5-10 mu M significantly increased cell viability and decreased lactate dehydrogenase release in A beta-treated BV-2 microglial cells. Western blotting analysis showed that S-aspirin suppressed the protein expression levels of cyclooxygenase-2 and growth arrest DNA damage (GADD). These data suggest that S-aspirin may protect microglial cells by inhibition of A beta-induced inflammation and cell cycle re-entry. To study whether S-aspirin can protect mitochondria function, mitochondria membrane potential was measured with molecular probe JC-1. It was found that S-aspirin protected mitochondria from A beta-induced loss of mitochondrial member potential. (Delta Psi m). In addition, S-aspirin also prevented A beta-induced activation of p38-mitogen activated protein kinase (MAPK). In conclusion, our results suggest that S-aspirin may protect microglial injury via inhibition of inflammation, prevention of mitochondria function, and stimulation of cell growth via stimulating p38-MAPK pathway. Our study may suggest that S-aspirin may have potential therapeutic value for the treatment of Alzheimer's disease. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.