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HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model

  • Authors:
    • Jun Li
    • Tao Tao
    • Jian Xu
    • Zhi Liu
    • Zhehua Zou
    • Minglu Jin
  • View Affiliations / Copyright

    Affiliations: Department of Rehabilitation Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Department of Neurology, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou 550001, P.R. China, Department of Pharmacy, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou 550001, P.R. China, Department of General Practice, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei 066000, P.R. China, Department of Neurology, Qijiang Hospital of The First Affiliated Hospital of Chongqing Medical University, Chongqing 404100, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1027-1036
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    Published online on: January 28, 2020
       https://doi.org/10.3892/ijmm.2020.4480
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Abstract

Hypoxia‑inducible factor‑1α (HIF‑1α) is a key transcriptional factor in response to hypoxia and is involved in ischemic stroke. In the present study, the potential for HIF‑1α to inhibit neuronal apoptosis through upregulating erythropoietin (EPO) was investigated in a transient middle cerebral artery occlusion (tMCAO) rat stroke model. For this purpose, a recombinant adenovirus expressing HIF‑1α was engineered (Ad‑HIF‑1α). Control adenovirus (Ad group), Ad‑HIF‑1α (Ad‑HIF‑1α group) or Ad‑HIF‑1α in addition to erythropoietin mimetic peptide‑9 (EMP9), an EPO‑receptor (‑R) antagonist (Ad‑HIF‑1α+EMP9 group), were used for an intracranial injection into rat ischemic penumbra 1 h following MCAO. All rats demonstrated functional improvement following tMCAO, while the improvement rate was faster in rats treated by Ad‑HIF‑1α compared with all other groups. The EPO‑R inhibitor partially reversed the benefits of Ad‑HIF‑1α. Apoptosis induced by tMCAO was significantly inhibited by Ad‑HIF‑1α (P<0.05). The expression of HIF‑1α, evaluated by immunohistochemistry either in neurons or astrocytes, was upregulated by Ad‑HIF‑1α. Both EPO mRNA and protein expression were increased by Ad‑HIF‑1α, however, there was no significant change of EPO‑R either on an mRNA level or protein level. Furthermore, EMP9 did not change the EPO expression which was upregulated by Ad‑HIF‑1α. Activated caspase 3 in neurons was suppressed by Ad‑HIF‑1α. Activated caspase 3 downregulated by HIF‑1α was partially blocked by EMP9. Altogether, the present data demonstrated that HIF‑1α attenuates neuronal apoptosis partially through upregulating EPO following cerebral ischemia in rat. Thus, upregulating HIF‑1α subsequent to a stroke may be a potential treatment for ischemic stroke.
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Copy and paste a formatted citation
Spandidos Publications style
Li J, Tao T, Xu J, Liu Z, Zou Z and Jin M: HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model. Int J Mol Med 45: 1027-1036, 2020.
APA
Li, J., Tao, T., Xu, J., Liu, Z., Zou, Z., & Jin, M. (2020). HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model. International Journal of Molecular Medicine, 45, 1027-1036. https://doi.org/10.3892/ijmm.2020.4480
MLA
Li, J., Tao, T., Xu, J., Liu, Z., Zou, Z., Jin, M."HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model". International Journal of Molecular Medicine 45.4 (2020): 1027-1036.
Chicago
Li, J., Tao, T., Xu, J., Liu, Z., Zou, Z., Jin, M."HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model". International Journal of Molecular Medicine 45, no. 4 (2020): 1027-1036. https://doi.org/10.3892/ijmm.2020.4480
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Tao T, Xu J, Liu Z, Zou Z and Jin M: HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model. Int J Mol Med 45: 1027-1036, 2020.
APA
Li, J., Tao, T., Xu, J., Liu, Z., Zou, Z., & Jin, M. (2020). HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model. International Journal of Molecular Medicine, 45, 1027-1036. https://doi.org/10.3892/ijmm.2020.4480
MLA
Li, J., Tao, T., Xu, J., Liu, Z., Zou, Z., Jin, M."HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model". International Journal of Molecular Medicine 45.4 (2020): 1027-1036.
Chicago
Li, J., Tao, T., Xu, J., Liu, Z., Zou, Z., Jin, M."HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model". International Journal of Molecular Medicine 45, no. 4 (2020): 1027-1036. https://doi.org/10.3892/ijmm.2020.4480
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