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BMC Anesthesiology
Published in: BMC Anesthesiology 1/2017

Open Access 01-12-2017 | Research article

The protective effects of propofol against CoCl2-induced HT22 cell hypoxia injury via PP2A/CAMKIIα/nNOS pathway

Authors: Yan Lu, Wei Chen, Chen Lin, Jiaqiang Wang, Minmin Zhu, Jiawei Chen, Changhong Miao

Published in: BMC Anesthesiology | Issue 1/2017

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Abstract

Background

Perioperative cerebral ischemia/hypoxia could induce hippocampal injury and has been reported to induce cognitive impairment. In this study, we used cobalt chloride (CoCl2) to build a hypoxia model in mouse hippocampal cell lines. Propofol, a widely used intravenous anesthetic agent, has been demonstrated to have neuroprotective effect. Here, we explored whether and how propofol attenuated CoCl2-induced mouse hippocampal HT22 cell injury.

Methods

Mouse hippocampal HT22 cells were pretreated with propofol, and then stimulated with CoCl2. Cell viability was measured by cell counting kit 8 (CCK8). The effect of propofol on CoCl2-modulated expressions of B-cell lymphoma 2 (Bcl-2), BAX, cleaved caspase 3, phosphatase A2 (PP2A), and the phosphorylation of Ca2+/Calmodulin (CaM)-dependent protein kinase II (pCAMKIIα), neuron nitric oxide synthase at Ser1412 (pnNOS-Ser1412), neuron nitric oxide synthase at Ser847 (pnNOS-Ser847) were detected by Western blot analysis.

Results

Compared with control, CoCl2 treatment could significantly decrease cell viability, which could be reversed by propofol. Further, we found CoCl2 treatment could up-regulate the expression of PP2A, BAX, cleaved caspase three and cause the phosphorylation of nNOS-Ser1412, but it down-regulated the expression of Bcl-2 and the phosphorylation of CAMKIIα and nNOS-Ser847. More importantly, these CoCl2-mediated effects were attentuated by propofol. In addition, we demonstrated that propofol could exert similar effect to that of the PP2A inhibitor (okadaic acid). Further, the PP2A activator (FTY720) and the CAMKIIα inhibitor (KN93) could reverse the neuroprotective effect of propofol.

Conclusion

Our data indicated that propofol could attenuate CoCl2-induced HT22 cells hypoxia injury via PP2A/CAMKIIα/nNOS pathway.
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Metadata
Title
The protective effects of propofol against CoCl2-induced HT22 cell hypoxia injury via PP2A/CAMKIIα/nNOS pathway
Authors
Yan Lu
Wei Chen
Chen Lin
Jiaqiang Wang
Minmin Zhu
Jiawei Chen
Changhong Miao
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2017
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-017-0327-1

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