H2S releasing aspirin protects amyloid beta induced cell toxicity in BV-2 microglial cells

β-Amyloid (Aβ) 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 Aβ-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 μM significantly increased cell viability and decreased lactate dehydrogenase release in Aβ-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 Aβ-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 Aβ-induced loss of mitochondrial member potential. (ΔΨm). In addition, S-aspirin also prevented Aβ-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.

Research highlights▶S-aspirin, but not aspirin, significantly increased cell viability in BV-2 microglial cells. ▶S-aspirin significantly attenuated Aβ-stimulated productions of nitric oxide and TNF-α. ▶S-aspirin protected mitochondria from Aβ-induced loss of membrane potential (ΔΨm). ▶S-aspirin prevented Aβ-induced activation of p38-mitogen activated protein kinase (MAPK), but not that of JNK and ERK.Figure optionsDownload high-quality image (200 K)Download as PowerPoint slide