Open Access

HIF‑α/PKM2 and PI3K‑AKT pathways involved in the protection by dexmedetomidine against isoflurane or bupivacaine‑induced apoptosis in hippocampal neuronal HT22 cells

  • Authors:
    • Fangping Bao
    • Xianhui Kang
    • Qing Xie
    • Jian Wu
  • View Affiliations

  • Published online on: November 12, 2018     https://doi.org/10.3892/etm.2018.6956
  • Pages: 63-70
  • Copyright: © Bao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated the mechanism underlying the protective effect of dexmedetomidine (Dex) on hippocampal neuronal HT22 cell apoptosis induced by the anesthetics isoflurane and bupivacaine. The cellular morphology was observed using a phase contrast microscope. The effects of anesthetics on cell proliferation were assayed using a Cell Counting Kit‑8 (CCK‑8). The levels of apoptosis were examined by flow cytometry utilizing Annexin V‑fluorescein isothiocyanate/propidium iodide double staining, and the protein expression levels of cleaved caspase‑3, phosphorylated phosphoinositide 3'‑kinase (p‑PI3K), p‑protein kinase B (p‑AKT), hypoxia inducible factor (HIF‑α), pyruvate kinase M2 (PKM2), B‑cell lymphoma (Bcl‑2)‑associated X protein (Bax), Bcl‑2 and cytochrome c were detected by western blot analysis. In vitro treatment with anesthetics was identified to decrease cell proliferation (P<0.01), the effect of which was then markedly inhibited by treatment with Dex (P<0.01) or a PI3K/AKT agonist. Exposure to anesthetics induced apoptosis in HT22 cells (75.4%), which was significantly attenuated by co‑treatment with Dex (26.2%) or the PI3K/AKT agonist (28.1%). Analysis of the protein expression levels revealed that exposure to anesthetics resulted in the activation of cleaved caspase‑3, Bax, cytochrome c, HIF‑α and PKM2 and decreased the expression levels of Bcl‑2, p‑PI3K and p‑AKT. However, these changes were inhibited by treatment with Dex or the PI3K/AKT agonist. Dex protected hippocampal neuronal HT22 cells from anesthetic‑induced apoptosis through the promotion of the PI3K/AKT pathway and inhibition of the HIF‑α/PKM2 axis.
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January-2019
Volume 17 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Bao F, Kang X, Xie Q and Wu J: HIF‑α/PKM2 and PI3K‑AKT pathways involved in the protection by dexmedetomidine against isoflurane or bupivacaine‑induced apoptosis in hippocampal neuronal HT22 cells. Exp Ther Med 17: 63-70, 2019
APA
Bao, F., Kang, X., Xie, Q., & Wu, J. (2019). HIF‑α/PKM2 and PI3K‑AKT pathways involved in the protection by dexmedetomidine against isoflurane or bupivacaine‑induced apoptosis in hippocampal neuronal HT22 cells. Experimental and Therapeutic Medicine, 17, 63-70. https://doi.org/10.3892/etm.2018.6956
MLA
Bao, F., Kang, X., Xie, Q., Wu, J."HIF‑α/PKM2 and PI3K‑AKT pathways involved in the protection by dexmedetomidine against isoflurane or bupivacaine‑induced apoptosis in hippocampal neuronal HT22 cells". Experimental and Therapeutic Medicine 17.1 (2019): 63-70.
Chicago
Bao, F., Kang, X., Xie, Q., Wu, J."HIF‑α/PKM2 and PI3K‑AKT pathways involved in the protection by dexmedetomidine against isoflurane or bupivacaine‑induced apoptosis in hippocampal neuronal HT22 cells". Experimental and Therapeutic Medicine 17, no. 1 (2019): 63-70. https://doi.org/10.3892/etm.2018.6956