[1]Massachusetts General Hospital and Harvard Medical School, Department of Anesthesiology,Boston,United States
[2]s Liberation Army, Anesthesia and Operation Center,Beijing,China
[3]Massachusetts General Hospital, Department of Anesthesiology,Boston,United States
[4]Massachusetts General Hospital and Harvard Medical School, Department of Anesthesia, Critical Care and Pain Medicine,Boston,United States
[5]Huazhong University of Science and Technology, Department of Medical Genetics,Wuhan,China
[6]Fudan University Shanghai Medical College, Department of Anesthesiology,Shanghai,China
[7]Capital Medical University China, Department of Anesthesiology,Beijing,China
[8]Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine,Boston,United States
Background: β-Amyloid protein (Aβ) has been shown to potentiate the caspase-3 activation induced by the commonly used inhalation anesthetic isoflurane. However, it is unknown whether reduction in Aβ levels can attenuate the isoflurane-induced caspase-3 activation. We therefore set out to determine the effects of RNA interference-mediated silencing of amyloid precursor protein (APP) and β-site APP-cleaving enzyme (BACE) on the levels of Aβ and the isoflurane-induced caspase-3 activation. Methods. H4 human neuroglioma cells stably transfected to express full-length human APP (H4-APP cells) were treated with small interference RNAs (siRNAs) targeted at silencing BACE and APP for 48 hours. The cells were then treated with 2% isoflurane for six hours. The levels of BACE, APP, and caspase-3 were determined using Western blot analysis. Sandwich Enzyme-linked immunosorbent assay (ELISA) was used to determine the extracellular Aβ levels in the conditioned cell culture media. Results: Here we show for the first time that treatment with BACE and APP siRNAs can decrease levels of BACE, full-length APP, and APP c-terminal fragments. Moreover, the treatment attenuates the Aβ levels and the isoflurane-induced caspase-3 activation. These results further suggest a potential role of Aβ in the isoflurane-induced caspase-3 activation such that the reduction in Aβ levels attenuates the isoflurane-induced caspase-3 activation. Conclusion: These findings will lead to more studies which aim at illustrating the underlying mechanism by which isoflurane and other anesthetics may affect Alzheimer"s disease neuropathogenesis. © 2011 Dong et al; licensee BioMed Central Ltd.
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