title: H2S releasing aspirin protects amyloid beta induced cell toxicity in BV-2 microglial cells.
abstract: 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 (H(2)S)-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 H(2)S. 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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Sparatore
authors.forename: P
authors.initials: P
authors.lastname: Del Soldato
authors.forename: J-S
authors.initials: JS
authors.lastname: Bian
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D045022:Lactate Dehydrogenases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D051742:Transcription Factor CHOP / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D020011:Protective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C078592:amyloid beta-protein (1-40); D051742:Transcription Factor CHOP; D009569:Nitric Oxide; D045022:Lactate Dehydrogenases; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; C022616:thiazolyl blue; D001241:Aspirin; D006862:Hydrogen Sulfide