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RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation

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 t...

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Autores principales: Dong, Yuanlin, Xu, Zhipeng, Zhang, Yiying, McAuliffe, Sayre, Wang, Hui, Shen, Xia, Yue, Yun, Xie, Zhongcong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191487/
https://www.ncbi.nlm.nih.gov/pubmed/22146340
http://dx.doi.org/10.1186/2045-9912-1-5
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author Dong, Yuanlin
Xu, Zhipeng
Zhang, Yiying
McAuliffe, Sayre
Wang, Hui
Shen, Xia
Yue, Yun
Xie, Zhongcong
author_facet Dong, Yuanlin
Xu, Zhipeng
Zhang, Yiying
McAuliffe, Sayre
Wang, Hui
Shen, Xia
Yue, Yun
Xie, Zhongcong
author_sort Dong, Yuanlin
collection PubMed
description 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.
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spelling pubmed-31914872011-12-01 RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation Dong, Yuanlin Xu, Zhipeng Zhang, Yiying McAuliffe, Sayre Wang, Hui Shen, Xia Yue, Yun Xie, Zhongcong Med Gas Res Research 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. BioMed Central 2011-04-28 /pmc/articles/PMC3191487/ /pubmed/22146340 http://dx.doi.org/10.1186/2045-9912-1-5 Text en Copyright ©2011 Dong et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Dong, Yuanlin
Xu, Zhipeng
Zhang, Yiying
McAuliffe, Sayre
Wang, Hui
Shen, Xia
Yue, Yun
Xie, Zhongcong
RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation
title RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation
title_full RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation
title_fullStr RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation
title_full_unstemmed RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation
title_short RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation
title_sort rna interference-mediated silencing of bace and app attenuates the isoflurane-induced caspase activation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191487/
https://www.ncbi.nlm.nih.gov/pubmed/22146340
http://dx.doi.org/10.1186/2045-9912-1-5
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