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Article

Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line

  • Authors:
    • Sun Young Park
    • Won Jung Jung
    • Jum Soon Kang
    • Cheol-Min Kim
    • Geuntae Park
    • Young-Whan Choi
  • View Affiliations / Copyright

    Affiliations: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea, Department of Horticultural Bioscience, Pusan National University, Miryang 627-706, Republic of Korea, Research Center for Anti-Aging Technology Development, Pusan National University, Busan 609-735, Republic of Korea
  • Pages: 525-532
    |
    Published online on: December 10, 2014
       https://doi.org/10.3892/ijmm.2014.2031
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Abstract

Since oxidative stress is critically involved in excitotoxic damage, we sought to determine whether the activation of the transcription factors, cAMP-responsive element binding protein (CREB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2, also known as NFE2L2), by α-iso-cubebene is involved in its protective effects against glutamate-induced neuronal cell death. Pre-treatment with α-iso-cubebene significantly attenuated glutamate-induced cytotoxicity in mouse hippocampus-derived neuronal cells. α-iso-cubebene also reduced the glutamate-induced generation of reactive oxygen species and calcium influx, thus preventing apoptotic cell death. α-iso-cubebene inhibited glutamate-induced mitochondrial membrane depolarization and, consequently, inhibited the release of the apoptosis-inducing factor from the mitochondria. Immunoblot anlaysis revealed that the phosphorylation of extracellular signal-regulated kinase (ERK) by glutamate was reduced in the presence of α-iso-cubebene. α-iso-cubebene activated protein kinase A (PKA), CREB and Nrf2, which mediate the expression of the antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1), involved in neuroprotection. In addition, α-iso-cubebene induced the expression of antioxidant responsive element and CRE transcriptional activity, thus conferring neuroprotection against glutamate-induced oxidative injury. α-iso-cubebene also induced the expression of Nrf2-dependent genes encoding HO-1 and NQO1. Furthermore, the knockdown of CREB and Nrf2 by small interfering RNA attenuated the neuroprotective effects of α-iso-cubebene. Taken together, our results indicate that α-iso-cubebene protects HT22 cells from glutamate-induced oxidative damage through the activation of Nrf2/HO-1/NQO-1, as well as through the PKA and CREB signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Park SY, Jung WJ, Kang JS, Kim C, Park G and Choi Y: Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line. Int J Mol Med 35: 525-532, 2015.
APA
Park, S.Y., Jung, W.J., Kang, J.S., Kim, C., Park, G., & Choi, Y. (2015). Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line. International Journal of Molecular Medicine, 35, 525-532. https://doi.org/10.3892/ijmm.2014.2031
MLA
Park, S. Y., Jung, W. J., Kang, J. S., Kim, C., Park, G., Choi, Y."Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line". International Journal of Molecular Medicine 35.2 (2015): 525-532.
Chicago
Park, S. Y., Jung, W. J., Kang, J. S., Kim, C., Park, G., Choi, Y."Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line". International Journal of Molecular Medicine 35, no. 2 (2015): 525-532. https://doi.org/10.3892/ijmm.2014.2031
Copy and paste a formatted citation
x
Spandidos Publications style
Park SY, Jung WJ, Kang JS, Kim C, Park G and Choi Y: Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line. Int J Mol Med 35: 525-532, 2015.
APA
Park, S.Y., Jung, W.J., Kang, J.S., Kim, C., Park, G., & Choi, Y. (2015). Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line. International Journal of Molecular Medicine, 35, 525-532. https://doi.org/10.3892/ijmm.2014.2031
MLA
Park, S. Y., Jung, W. J., Kang, J. S., Kim, C., Park, G., Choi, Y."Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line". International Journal of Molecular Medicine 35.2 (2015): 525-532.
Chicago
Park, S. Y., Jung, W. J., Kang, J. S., Kim, C., Park, G., Choi, Y."Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line". International Journal of Molecular Medicine 35, no. 2 (2015): 525-532. https://doi.org/10.3892/ijmm.2014.2031
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