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Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells

  • Authors:
    • Jianyu Wang
    • Yuankang Zou
    • Ruili Guan
    • Shuangshuang Tan
    • Lihong Su
    • Zaihua Zhao
    • Zipeng Cao
    • Kunyan Jiang
    • Tao Wang
    • Gang Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Occupational and Environmental Health and the Ministry‑of‑Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Preventive Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 117
    |
    Published online on: October 18, 2024
       https://doi.org/10.3892/ijmm.2024.5441
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Abstract

Hypoxic ischemia is the primary cause of brain damage in newborns. Notably, copper supplementation has potential benefits in ischemic brain damage; however, the precise mechanisms underlying this protective effect remain unclear. In the present study, a hypoxic HT22 cell model was developed to examine the mechanism by which copper mitigates hypoxia‑induced oxidative stress. Cell viability was assessed using the Cell Counting Kit‑8 assay, mitochondrial structure was examined with a transmission electron microscope, intracellular ferrous ions and lipid reactive oxygen species levels in HT22 cells were measured using FerroOrange and BODIPY 581/591 C11 staining, copper content was determined using graphite furnace atomic absorption spectroscopy, and gene and protein expression were analyzed by reverse transcription‑quantitative PCR and western blotting. The present findings indicated that hypoxic exposure may lead to reduced cell viability, along with the upregulation of various markers associated with ferroptosis. Furthermore, hypoxia elevated the levels of reactive oxygen species, hydrogen peroxide and malondialdehyde, and decreased the activity of superoxide dismutase 1 (SOD1) in HT22 cells. In addition, the intracellular copper concentration exhibited a notable decrease, while supplementation with an appropriate dose of copper effectively shielded neurons from hypoxia‑induced oxidative stress and ferroptosis, and elevated cell viability in hypoxia‑exposed HT22 cells through the copper chaperone for superoxide dismutase/SOD1/glutathione peroxidase 4 axis. In conclusion, the present study identified a novel function of copper in protecting neurons from oxidative stress and ferroptosis under hypoxic conditions, providing fresh insights into the therapeutic potential of copper in mitigating hypoxia‑induced neuronal injury.
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Copy and paste a formatted citation
Spandidos Publications style
Wang J, Zou Y, Guan R, Tan S, Su L, Zhao Z, Cao Z, Jiang K, Wang T, Zheng G, Zheng G, et al: Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells. Int J Mol Med 54: 117, 2024.
APA
Wang, J., Zou, Y., Guan, R., Tan, S., Su, L., Zhao, Z. ... Zheng, G. (2024). Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells. International Journal of Molecular Medicine, 54, 117. https://doi.org/10.3892/ijmm.2024.5441
MLA
Wang, J., Zou, Y., Guan, R., Tan, S., Su, L., Zhao, Z., Cao, Z., Jiang, K., Wang, T., Zheng, G."Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells". International Journal of Molecular Medicine 54.6 (2024): 117.
Chicago
Wang, J., Zou, Y., Guan, R., Tan, S., Su, L., Zhao, Z., Cao, Z., Jiang, K., Wang, T., Zheng, G."Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells". International Journal of Molecular Medicine 54, no. 6 (2024): 117. https://doi.org/10.3892/ijmm.2024.5441
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Zou Y, Guan R, Tan S, Su L, Zhao Z, Cao Z, Jiang K, Wang T, Zheng G, Zheng G, et al: Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells. Int J Mol Med 54: 117, 2024.
APA
Wang, J., Zou, Y., Guan, R., Tan, S., Su, L., Zhao, Z. ... Zheng, G. (2024). Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells. International Journal of Molecular Medicine, 54, 117. https://doi.org/10.3892/ijmm.2024.5441
MLA
Wang, J., Zou, Y., Guan, R., Tan, S., Su, L., Zhao, Z., Cao, Z., Jiang, K., Wang, T., Zheng, G."Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells". International Journal of Molecular Medicine 54.6 (2024): 117.
Chicago
Wang, J., Zou, Y., Guan, R., Tan, S., Su, L., Zhao, Z., Cao, Z., Jiang, K., Wang, T., Zheng, G."Copper supplementation alleviates hypoxia‑induced ferroptosis and oxidative stress in neuronal cells". International Journal of Molecular Medicine 54, no. 6 (2024): 117. https://doi.org/10.3892/ijmm.2024.5441
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