Anesthetic Propofol Attenuates the Isoflurane-Induced Caspase-3 Activation and Aβ Oligomerization
Open Access
- 1 November 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (11), e27019
- https://doi.org/10.1371/journal.pone.0027019
Abstract
Accumulation and deposition of β-amyloid protein (Aβ) are the hallmark features of Alzheimer's disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase Aβ accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble Aβ oligomers, which are thought to be the key pathological species in AD. In contrast, propofol, the most commonly used intravenous anesthetic, has been reported to have neuroprotective effects. We therefore set out to compare the effects of isoflurane and propofol alone and in combination on caspase-3 activation and Aβ oligomerization in vitro and in vivo. Naïve and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for Aβ; neonatal mice; and conditioned cell culture media containing secreted human Aβ40 or Aβ42 were treated with isoflurane and/or propofol. Here we show for the first time that propofol can attenuate isoflurane-induced caspase-3 activation in cultured cells and in the brain tissues of neonatal mice. Furthermore, propofol-mediated caspase inhibition occurred when there were elevated levels of Aβ. Finally, isoflurane alone induces Aβ42, but not Aβ40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of Aβ42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced Aβ42 oligomerization. Our findings provide novel insights into the possible mechanisms of isoflurane-induced neurotoxicity that may aid in the development of strategies to minimize potential adverse effects associated with the administration of anesthetics to patients.This publication has 48 references indexed in Scilit:
- Effects of propofol on proliferation and anti-apoptosis of neuroblastoma SH-SY5Y cell line: New insights into neuroprotectionBrain Research, 2011
- Anesthetic Sevoflurane Causes Neurotoxicity Differently in Neonatal Naïve and Alzheimer Disease Transgenic MiceAnesthesiology, 2010
- The Mitochondrial Pathway of Anesthetic Isoflurane-induced ApoptosisOnline Journal of Public Health Informatics, 2010
- Alzheimer's DiseaseThe New England Journal of Medicine, 2010
- Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesiaThe FASEB Journal, 2009
- Propofol: neuroprotection in an in vitro model of traumatic brain injuryCritical Care, 2009
- The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid β‐protein level in vivoAnnals of Neurology, 2008
- Depletion of GGA3 Stabilizes BACE and Enhances β-Secretase ActivityNeuron, 2007
- Aβ42 is More Rigid than Aβ40 at the C Terminus: Implications for Aβ Aggregation and ToxicityJournal of Molecular Biology, 2006
- Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell linesLife Sciences, 2005