Abstract
BackgroundPerioperative 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.MethodsMouse 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.ResultsCompared 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.ConclusionOur data indicated that propofol could attenuate CoCl2-induced HT22 cells hypoxia injury via PP2A/CAMKIIα/nNOS pathway.
Highlights
Perioperative cerebral ischemia/hypoxia could induce hippocampal injury and has been reported to induce cognitive impairment
Cobalt chloride (CoCl2) induced HT22 cell injury, which was attenuated by propofol In HT22 cells, 500 μM CoCl2 treatment induced cell injury in a time-dependent manner
We demonstrated that CoCl2 (500 μM, 12 h) treatment decreased the expression of pCAMKIIα by 50% (p < 0.05, Fig. 3a, d), which was reversed by 25 μM propofol treatment (p < 0.05, Fig. 3a, d)
Summary
Perioperative cerebral ischemia/hypoxia could induce hippocampal injury and has been reported to induce cognitive impairment. We used cobalt chloride (CoCl2) to build a hypoxia model in mouse hippocampal cell lines. We explored whether and how propofol attenuated CoCl2-induced mouse hippocampal HT22 cell injury. Previous study has demonstrated that CAMKIIα could be dephosphorylated by PP2A, leading to a reduction of its enzyme activity [11]. Inhibition of the activity of PP2A may protect hippocampal cells from injury in vitro. Propofol has been demonstrated to be neuroprotective against oxide stress [15] and ischemia injury [16]. We used cobalt chloride (CoCl2) to build an in vitro hypoxia model and aimed to clarify whether and how propofol attenuated CoCl2-induced HT22 cell hypoxia injury
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