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Article

Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway

  • Authors:
    • Zi‑Ru Li
    • Lei Yang
    • Jin Zhen
    • Yan Zhao
    • Zu‑Neng Lu
  • View Affiliations / Copyright

    Affiliations: Department of Internal Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
  • Pages: 1470-1476
    |
    Published online on: June 20, 2018
       https://doi.org/10.3892/etm.2018.6330
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Abstract

Nobiletin (NOB) possesses multiple pharmacological effects, but its anti‑apoptotic property has acquired a great deal of attention. Endoplasmic reticulum (ER) stress (ERS)‑induced apoptosis acts as the pivotal aetiology in neuronal oxygen‑glucose deprivation and reoxygenation (OGD/R) injury. The aim of this study focused on whether NOB exerts neuro‑protective effects on OGD/R injury by repressing ERS‑induced apoptosis. The PC12 neuronal cell line was subjected to 4 h OGD and 24 h reoxygenation following NOB treatment. A PI3K/AKT inhibitor (LY294002) was added during the mechanistic experiments. Cell viability, lactate dehydrogenase (LDH) release and apoptosis were determined. Western blotting was used to measure protein expression levels. The results showed that OGD/R caused neuronal damageas exhibited by the increase in LDH release and the reduction of cellular viability. Moreover, ERS‑induced apoptosis was markedly stimulated by OGD/R in PC12 cells, as evidenced by the elevation in the apoptotic rate and protein levels of C/EBP homologous protein/glucose‑regulated protein‑78. However, NOB administration significantly reversed neuronal damage and the ERS‑induced apoptosis in response to OGD/R injury. Mechanistic detections showed that the neuron‑favorable and ERS‑repressing contributions of NOB were, in part, a result of the activation of the PI3K/AKT pathway, which was validated by a specific PI3K/AKT inhibitor (LY294002). Therefore, NOB protects PC12 cells from ERS‑induced apoptosis in OGD/R injury mainly through enhancement of the PI3K/AKT pathway, which may provide a novel therapeutic avenue for the prevention of cerebral ischemia/reperfusion injury.
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Copy and paste a formatted citation
Spandidos Publications style
Li ZR, Yang L, Zhen J, Zhao Y and Lu ZN: Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway. Exp Ther Med 16: 1470-1476, 2018.
APA
Li, Z., Yang, L., Zhen, J., Zhao, Y., & Lu, Z. (2018). Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway. Experimental and Therapeutic Medicine, 16, 1470-1476. https://doi.org/10.3892/etm.2018.6330
MLA
Li, Z., Yang, L., Zhen, J., Zhao, Y., Lu, Z."Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway". Experimental and Therapeutic Medicine 16.2 (2018): 1470-1476.
Chicago
Li, Z., Yang, L., Zhen, J., Zhao, Y., Lu, Z."Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway". Experimental and Therapeutic Medicine 16, no. 2 (2018): 1470-1476. https://doi.org/10.3892/etm.2018.6330
Copy and paste a formatted citation
x
Spandidos Publications style
Li ZR, Yang L, Zhen J, Zhao Y and Lu ZN: Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway. Exp Ther Med 16: 1470-1476, 2018.
APA
Li, Z., Yang, L., Zhen, J., Zhao, Y., & Lu, Z. (2018). Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway. Experimental and Therapeutic Medicine, 16, 1470-1476. https://doi.org/10.3892/etm.2018.6330
MLA
Li, Z., Yang, L., Zhen, J., Zhao, Y., Lu, Z."Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway". Experimental and Therapeutic Medicine 16.2 (2018): 1470-1476.
Chicago
Li, Z., Yang, L., Zhen, J., Zhao, Y., Lu, Z."Nobiletin protects PC12 cells from ERS‑induced apoptosis in OGD/R injury via activation of the PI3K/AKT pathway". Experimental and Therapeutic Medicine 16, no. 2 (2018): 1470-1476. https://doi.org/10.3892/etm.2018.6330
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