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Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and A? oligomerization.


ABSTRACT: Accumulation and deposition of ?-amyloid protein (A?) are the hallmark features of Alzheimer's disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase A? accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble A? 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 A? oligomerization in vitro and in vivo. Naïve and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for A?; neonatal mice; and conditioned cell culture media containing secreted human A?40 or A?42 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 A?. Finally, isoflurane alone induces A?42, but not A?40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of A?42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced A?42 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.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC3206055 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and Aβ oligomerization.

Zhang Yiying Y   Zhen Yu Y   Dong Yuanlin Y   Xu Zhipeng Z   Yue Yun Y   Golde Todd E TE   Tanzi Rudolph E RE   Moir Robert D RD   Xie Zhongcong Z  

PloS one 20111101 11


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 neuropr  ...[more]

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