Hypoxia-regulated neurotrophin-3 expression by multicopy hypoxia response elements reduces apoptosis in PC12 cells

  • Authors:
    • Junfeng Zhang
    • Qindong Shi
    • Xinlin Chen
    • Pengbo Yang
    • Cunfang Qi
    • Jianshui Zhang
    • Haixia Lu
    • Jianxin Liu
    • Qian Jiao
    • Lingyu Zhao
    • Bingqiao Zhao
    • Ping Zheng
    • Yong Liu
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  • Published online on: September 6, 2012     https://doi.org/10.3892/ijmm.2012.1119
  • Pages: 1173-1179
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Abstract

We have previously reported that 5 copies of the hypoxia response element (HRE) can conditionally regulate brain-derived neurotrophic factor gene expression under hypoxic/ischemic conditions in mice. In the present study, we investigated the controlled expression of neurotrophin-3 (NT-3) by HRE under hypoxic conditions and determined the protective effects of conditionally expressed NT-3 on hypoxia-induced apoptosis in PC12 cells. Five copies of the HRE (5HRE) and the simian virus 40 minimal promoter (SV40mp) were employed to construct a cassette, and transfer of therapeutic gene, NT-3, into PC12 cells was achieved using a retroviral vector. Our results showed that the retroviral vector, pLNC-5HRE-NT3, was successfully constructed and transfected into PC12 cells. Compared with normal conditions, in which NT-3 was expressed at low levels, the expression of NT-3 significantly increased under hypoxic conditions in 5HRE-NT3 transgenic PC12 cells (P<0.05). By contrast, in NT-3 transgenic PC12 cells without HRE, we found no significant difference in NT-3 expression between the normoxic and hypoxic groups. The conditional adjustment of NT-3 expression by 5HRE significantly reduced apoptosis induced by hypoxia in 5HRE-NT3 transgenic PC12 cells (P<0.05) but not in 5HRE-enhanced green fluorescent protein (EGFP) transgenic PC12 cells and PC12 cells without gene transfer. In addition, the hypoxia-induced upregulation of both p38 and caspase-3 activities was suppressed in 5HRE-NT3 transgenic PC12 cells under hypoxic conditions (P<0.05). Taken together, these results demonstrate that 5HRE-SV40mp regulates NT-3 gene expression in response to hypoxia in PC12 cells. The data presented in this study may prove useful in future gene therapy studies for the treatment of ischemic diseases.
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November 2012
Volume 30 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang J, Shi Q, Chen X, Yang P, Qi C, Zhang J, Lu H, Liu J, Jiao Q, Zhao L, Zhao L, et al: Hypoxia-regulated neurotrophin-3 expression by multicopy hypoxia response elements reduces apoptosis in PC12 cells. Int J Mol Med 30: 1173-1179, 2012
APA
Zhang, J., Shi, Q., Chen, X., Yang, P., Qi, C., Zhang, J. ... Liu, Y. (2012). Hypoxia-regulated neurotrophin-3 expression by multicopy hypoxia response elements reduces apoptosis in PC12 cells. International Journal of Molecular Medicine, 30, 1173-1179. https://doi.org/10.3892/ijmm.2012.1119
MLA
Zhang, J., Shi, Q., Chen, X., Yang, P., Qi, C., Zhang, J., Lu, H., Liu, J., Jiao, Q., Zhao, L., Zhao, B., Zheng, P., Liu, Y."Hypoxia-regulated neurotrophin-3 expression by multicopy hypoxia response elements reduces apoptosis in PC12 cells". International Journal of Molecular Medicine 30.5 (2012): 1173-1179.
Chicago
Zhang, J., Shi, Q., Chen, X., Yang, P., Qi, C., Zhang, J., Lu, H., Liu, J., Jiao, Q., Zhao, L., Zhao, B., Zheng, P., Liu, Y."Hypoxia-regulated neurotrophin-3 expression by multicopy hypoxia response elements reduces apoptosis in PC12 cells". International Journal of Molecular Medicine 30, no. 5 (2012): 1173-1179. https://doi.org/10.3892/ijmm.2012.1119