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Título: | Correction: Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate Amyloid-β Peptide Generation In Vivo |
Autor: | Serrano-Pozo, Alberto; Sánchez García, Manuel A.; Heras-Garvin, Antonio CSIC ORCID; March Díaz, Rosana CSIC; Navarro-Garrido, Victoria CSIC; Vizuete, Marisa CSIC; López-Barneo, José CSIC ORCID; Vitorica, Javier CSIC ORCID; Pascual Bravo, Alberto CSIC ORCID | Fecha de publicación: | 26-jul-2017 | Editor: | Public Library of Science | Citación: | PLoS ONE (7): e0181510 (2017) | Resumen: | [Background] Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number of in vitro and in vivo studies have reported that hypoxia can induce amyloid-β peptide accumulation through various molecular mechanisms including the up-regulation of the amyloid-β precursor protein, the β-secretase Bace1, or the γγ-secretase complex components, as well as the down-regulation of Aβ-degrading enzymes. [Objectives] To investigate the effects of acute and chronic sustained hypoxia in Aβ generation in vivo. [Methods] 2–3 month-old C57/Bl6J wild-type mice were exposed to either normoxia (21% O2) or hypoxia (9% O2) for either 4 to 72 h (acute) or 21–30 days (chronic sustained) in a hermetic chamber. Brain mRNA levels of Aβ-related genes were measured by quantitative real-time PCR, whereas levels of Bace1 protein, full length AβPP, and its C-terminal fragments (C99/C88 ratio) were measured by Western blot. In addition, 8 and 14-month-old APP/PS1 transgenic mice were subjected to 9% O2 for 21 days and levels of Aβ40, Aβ42, full length AβPP, and soluble AβPPα (sAβPPα) were measured by ELISA or WB. [Results] Hypoxia (either acute or chronic sustained) did not impact the transcription of any of the Aβ-related genes in young wild-type mice. A significant reduction of Bace1 protein level was noted with acute hypoxia for 16 h but did not correlate with an increased level of full length AβPP or a decreased C99/C83 ratio. Chronic sustained hypoxia did not significantly alter the levels of Bace1, full length AβPP or the C99/C83 ratio. Last, chronic sustained hypoxia did not significantly change the levels of Aβ40, Aβ42, full length AβPP, or sAβPPα in either young or aged APP/PS1 mice. [Discussion] Our results argue against a hypoxia-induced shift of AβPP proteolysis from the non-amyloidogenic to the amyloidogenic pathways. We discuss the possible methodological caveats of previous in vivo studies. |
Descripción: | There are several errors throughout the paper. | Versión del editor: | https://doi.org/10.1371/journal.pone.0181510 | URI: | http://hdl.handle.net/10261/180686 | DOI: | 10.1371/journal.pone.0181510 | E-ISSN: | 1932-6203 | Referencias: | Serrano-Pozo, Alberto; Sánchez García, Manuel A.; Heras-Garvin, Antonio ; March Díaz, Rosana ; Navarro, Victoria; Vizuete, Marisa; López-Barneo, José ; Vitorica, Javier ; Pascual Bravo, Alberto. Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate Amyloid-β Peptide Generation In Vivo. https://doi.org/10.1371/journal.pone.0170345 http://hdl.handle.net/10261/180684 |
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