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Upregulation of HIF-1α protein induces mitochondrial autophagy in primary cortical cell cultures through the inhibition of the mTOR pathway

  • Authors:
    • Gu Gong
    • Ling Hu
    • Yinghai Liu
    • Shurong Bai
    • Xuemei Dai
    • Liang Yin
    • Yangyang Sun
    • Xiaowu Wang
    • Lichao Hou

  • View Affiliations

  • Published online on: July 14, 2014     https://doi.org/10.3892/ijmm.2014.1850
  • Pages: 1133-1140
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Cerebral ischemia/reperfusion (I/R) can induce neuronal death, particularly in the hippocampal formation (HF). Molecular genetic studies have suggested that the activities of the transcription factor, hypoxia-inducible factor-1α (HIF-1α), are closely linked to ischemia-induced neuronal death. However, the mechanisms through which HIF-1α functions remain poorly understood. In this study, primary cortical neurons were subjected to oxygen‑glucose deprivation (OGD) to establish a cell model of OGD/reperfusion (RP). HIF-1α mRNA and protein expression was measured by qRT-PCR and western blot analysis. Cell proliferation was detected by MTT assay. Flow cytometric analysis was used to detect cell apoptosis and changes in mitochondrial mass. The expression of LC3-Ⅰ and LC3-Ⅱ was examined by western blot analysis. We found that HIF-1α increased cell proliferation and decreased cell apoptosis in our cell model of OGD/RP using cultured neonatal rat cortical neurons. The overexpression of HIF-1α significantly induced changes in mitochondrial mass and mitochondrial autophagy in cortical neurons. Moreover, the inhibition of HIF-1α markedly suppressed cell proliferation and mitochondrial autophagy. We also demonstrated that the HIF-1α-induced mitochondrial autophagy was accompanied by the inhibition of the mTOR pathway. This study provides direct in vitro evidence that HIF-1α overexpression triggers mitochondrial autophagy, thereby increasing neuronal survival. Our results highlight a novel target molecule toward which anti-ischemic neuroprotective effects can be applied.
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October 2014
Volume 34 Issue 4

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

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  • Journal Metrics
  • Impact Factor: 5.4
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 10.7
  • CiteScore Rank: Q1: #35/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.994
  • SCImago Journal Rank (SJR): 0.922
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Spandidos Publications style
Gong G, Hu L, Liu Y, Bai S, Dai X, Yin L, Sun Y, Wang X and Hou L: Upregulation of HIF-1α protein induces mitochondrial autophagy in primary cortical cell cultures through the inhibition of the mTOR pathway. Int J Mol Med 34: 1133-1140, 2014
APA
Gong, G., Hu, L., Liu, Y., Bai, S., Dai, X., Yin, L. ... Hou, L. (2014). Upregulation of HIF-1α protein induces mitochondrial autophagy in primary cortical cell cultures through the inhibition of the mTOR pathway. International Journal of Molecular Medicine, 34, 1133-1140. https://doi.org/10.3892/ijmm.2014.1850
MLA
Gong, G., Hu, L., Liu, Y., Bai, S., Dai, X., Yin, L., Sun, Y., Wang, X., Hou, L."Upregulation of HIF-1α protein induces mitochondrial autophagy in primary cortical cell cultures through the inhibition of the mTOR pathway". International Journal of Molecular Medicine 34.4 (2014): 1133-1140.
Chicago
Gong, G., Hu, L., Liu, Y., Bai, S., Dai, X., Yin, L., Sun, Y., Wang, X., Hou, L."Upregulation of HIF-1α protein induces mitochondrial autophagy in primary cortical cell cultures through the inhibition of the mTOR pathway". International Journal of Molecular Medicine 34, no. 4 (2014): 1133-1140. https://doi.org/10.3892/ijmm.2014.1850