A mutation in β-amyloid precursor protein renders SH‑SY5Y cells vulnerable to isoflurane toxicity: The role of inositol 1,4,5‑trisphosphate receptors

Liu,Xiang; Song,Shan; Wang,Qiujun; Yuan,Tianbao; He,Jihua

doi:10.3892/mmr.2016.5930

A mutation in β-amyloid precursor protein renders SH‑SY5Y cells vulnerable to isoflurane toxicity: The role of inositol 1,4,5‑trisphosphate receptors

Authors:
- Xiang Liu
- Shan Song
- Qiujun Wang
- Tianbao Yuan
- Jihua He
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Affiliations: Department of Anesthesiology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei 050031, P.R. China, Department of Anesthesiology, Yantai Yu Huang Ding Hospital, Yantai, Shandong 264000, P.R. China, Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
Published online on: November 8, 2016 https://doi.org/10.3892/mmr.2016.5930
Pages: 5435-5442
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Isoflurane is a commonly used inhaled anesthetic, which induces apoptosis of SH‑SY5Y cells in a dose‑ and time‑dependent manner; however, the underlying mechanisms remain unknown. The authors of the present study hypothesized that a mutation in β‑amyloid precursor protein (APP), which is a gene associated with familial Alzheimer's disease, may render cells vulnerable to isoflurane‑induced cytotoxicity via activation of inositol 1,4,5‑trisphosphate receptors (IP3R). In the present study, SH‑SY5Y cells were transfected with a vector or with mutated APP, and were treated with the equivalent of 1 minimum alveolar concentration (MAC) isoflurane for 8 h. Cell apoptosis rate, alterations to cytosolic calcium concentrations ([Ca2+]c), and protein levels of IP3R were determined following exposure of cells to isoflurane. In addition, the effects of the IP3R antagonist xestospongin C were determined on isoflurane‑induced cytotoxicity and calcium release from the endoplasmic reticulum (ER) of mutated APP‑ and vector‑transfected SH‑SY5Y cells. Treatment with isoflurane (1 MAC) for 8 h induced a higher degree of cytotoxicity, and a marked increase in [Ca2+]c and IP3R protein levels in mutated APP‑transfected SH‑SY5Y cells compared with vector‑transfected SH‑SY5Y cells. Xestospongin C significantly attenuated isoflurane‑mediated cytotoxicity and inhibited calcium release from the ER of SH‑SY5Y cells. These results indicated that the APP mutation may render SH‑SY5Y cells vulnerable to isoflurane neurotoxicity, and the underlying mechanism may be associated with Ca2+ dysregulation via overactivation of IP3R.

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