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TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway

  • Authors:
    • Linglei Meng
    • Yongting Zhang
    • Demao Li
    • Xinfang Shang
    • Xuejia Hao
    • Xin Chen
    • Fengxiao Gao
  • View Affiliations / Copyright

    Affiliations: Department of Imaging, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China, Department of Imaging, Xingtai Orthopedic Hospital, Xingtai, Hebei 054001, P.R. China, Department of Cardiothoracic Surgery, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China, Department of Neurology, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China
    Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 973
    |
    Published online on: July 8, 2021
       https://doi.org/10.3892/etm.2021.10405
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Abstract

Ischemic stroke seriously threatens human health and creates a large social burden. The present study investigated whether tissue inhibitor of metalloproteinases‑3 (TIMP3) prevented cerebral ischemia/reperfusion (I/R), with the aim to explore the underlying mechanism. A transient middle cerebral artery occlusion model was conducted in mice, and oxygen glucose deprivation and reoxygenation (OGD/R) was investigated in PC12 cells to mimic cerebral ischemia‑reperfusion injury (CIRI). Western blotting was used to determine the expression of TIMP3, Bax, Bcl‑2 and AKT. TUNEL was used to detect apoptosis in cerebral tissues or cultured PC12 cells. Expression levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected to reveal oxidative stress. The results demonstrated that TIMP3 expression was significantly decreased after I/R in vivo or OGD/R in vitro, and the number of TUNEL‑positive cells was reduced by the overexpression of TIMP3. The attenuation of Bax/Bcl‑2 ratio in OGD/R‑induced PC12 cells suppressed the expression levels of ROS and MDA; while also elevating SOD activity in the OGD/R‑induced neurocytes in vitro. In addition, TIMP3‑overexpression reversed the downregulation of phosphorylated‑AKT (Thr308 and Ser473) in OGD/R‑treated PC12 cells. However, the anti‑apoptotic and anti‑oxidative stress roles of TIMP3 in OGD/R‑induced PC12 cells were partially abolished after treatment with the AKT inhibitor, AZD5363. Overall, TIMP3 exerted an anti‑apoptotic and anti‑oxidative stress role in CIRI through the AKT pathway, which may be a potential therapeutic target for the treatment of CIRI.
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Copy and paste a formatted citation
Spandidos Publications style
Meng L, Zhang Y, Li D, Shang X, Hao X, Chen X and Gao F: TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway. Exp Ther Med 22: 973, 2021.
APA
Meng, L., Zhang, Y., Li, D., Shang, X., Hao, X., Chen, X., & Gao, F. (2021). TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway. Experimental and Therapeutic Medicine, 22, 973. https://doi.org/10.3892/etm.2021.10405
MLA
Meng, L., Zhang, Y., Li, D., Shang, X., Hao, X., Chen, X., Gao, F."TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway". Experimental and Therapeutic Medicine 22.3 (2021): 973.
Chicago
Meng, L., Zhang, Y., Li, D., Shang, X., Hao, X., Chen, X., Gao, F."TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway". Experimental and Therapeutic Medicine 22, no. 3 (2021): 973. https://doi.org/10.3892/etm.2021.10405
Copy and paste a formatted citation
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Spandidos Publications style
Meng L, Zhang Y, Li D, Shang X, Hao X, Chen X and Gao F: TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway. Exp Ther Med 22: 973, 2021.
APA
Meng, L., Zhang, Y., Li, D., Shang, X., Hao, X., Chen, X., & Gao, F. (2021). TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway. Experimental and Therapeutic Medicine, 22, 973. https://doi.org/10.3892/etm.2021.10405
MLA
Meng, L., Zhang, Y., Li, D., Shang, X., Hao, X., Chen, X., Gao, F."TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway". Experimental and Therapeutic Medicine 22.3 (2021): 973.
Chicago
Meng, L., Zhang, Y., Li, D., Shang, X., Hao, X., Chen, X., Gao, F."TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway". Experimental and Therapeutic Medicine 22, no. 3 (2021): 973. https://doi.org/10.3892/etm.2021.10405
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