Abstract
Hippocampal neuronal oxidative stress and apoptosis have been reported to be involved in cognitive impairment, and angiotensin II could induce hippocampal oxidative stress and apoptosis. Propofol is a widely used intravenous anesthetic agent in clinical practice, and it demonstrates significant neuroprotective activities. In this study, we investigated the mechanism how propofol protected mouse hippocampal HT22 cells against angiotensin II-induced oxidative stress and apoptosis. Cell viability was evaluated with CCK8 kit. Protein expressions of active caspase 3, cytochrome c, p66Shc, p-p66shc–Ser36, protein kinase C βII (PKCβII), Pin-1 and phosphatase A2 (PP2A) were measured by Western blot. Superoxide anion (O .−2 ) accumulation was measured with the reduction of ferricytochrome c. Compared with the control group, angiotensin II up-regulated expression of PKCβII, Pin-1 and PP2A, induced p66Shc–Ser36 phosphorylation, and facilitated p66Shc mitochondrial translocation, resulting in O .−2 accumulation, mitochondrial cytochrome c release, caspase 3 activation, and the inhibition of cell viability. Importantly, we found propofol inhibited angiotensin II-induced PKCβII and PP2A expression and improved p66Shc mitochondrial translocation, O .−2 accumulation, mitochondrial cytochrome c release, caspase 3 activation, inhibition of cell viability. On the other hand, propofol had no effects on angiotensin II-induced Pin-1 expression and p66Shc–Ser36 phosphorylation. Moreover, the protective effects of propofol on angiotensin II-induced HT22 apoptosis were similar with calyculin A, an inhibitor of PP2A and CGP53353, an inhibitor of PKCβII. However, the protective effect of propofol could be reversed by FTY720, an activator of PP2A, rather than PMA, an activator of PKCβII. Our data indicated that propofol down-regulated PP2A expression, inhibiting dephosphorylation of p66Shc–Ser36 and p66Shc mitochondrial translocation, decreasing O .−2 accumulation, reducing mitochondrial cytochrome c release, inhibiting caspase 3 activation. By these mechanisms, it protects mouse hippocampal HT22 cells against angiotensin II-induced apoptosis.
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Zhu, M., Chen, J., Wen, M. et al. Propofol Protects Against Angiotensin II-Induced Mouse Hippocampal HT22 Cells Apoptosis Via Inhibition of p66Shc Mitochondrial Translocation. Neuromol Med 16, 772–781 (2014). https://doi.org/10.1007/s12017-014-8326-6
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DOI: https://doi.org/10.1007/s12017-014-8326-6