Ecto‑5'‑nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway

Shao,Minghao; Zheng,Chaojun; Ma,Xiaosheng; Lyu,Feizhou

doi:10.3892/etm.2021.10809

December-2021 Volume 22 Issue 6

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December-2021 Volume 22 Issue 6

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Article Open Access

Ecto‑5'‑nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway

Authors:
- Minghao Shao
- Chaojun Zheng
- Xiaosheng Ma
- Feizhou Lyu
View Affiliations / Copyright

Affiliations: Department of Spine Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China

Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 1374
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Published online on: September 28, 2021

https://doi.org/10.3892/etm.2021.10809
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Abstract

Spinal cord injury (SCI) is a serious affliction that can lead to insufficient blood supply to the spinal cord, resulting in nutrient and energy deficiency in nerve cells such as neurons. In the present study, a spinal cord injury mouse model was constructed using wild‑type (WT) and ecto‑5'‑nucleotidase (CD73)^‑/‑ mice. The results of TUNEL and immunofluorescence assays indicated that the apoptosis of neurons in CD73^‑/‑ mice was increased after spinal cord injury. Dorsal root ganglion (DRG) neurons from WT and CD73^‑/‑ mice were cultured in low glucose and hypoxic conditions to simulate the effects of spinal cord injury on neurons. Subsequently, a western blot assay was used to detect the expression of CD73, caspase‑3 and Bcl‑2. Flow cytometry was used to detect cell apoptosis and the corresponding kits were used to detect changes in lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), adenosine triphosphate (ATP) and cell activity. The results revealed that the apoptosis level of CD73‑overexpressing DRG neurons was decreased under anoxia and glucose deficiency. The release of LDH, MDA and the production of ROS in CD73 DRG neurons was decreased, while the synthesis of ATP, the activity of SOD and cell activity increased after hypoxia‑hypoglycemia treatment. Additional cellular studies demonstrated that blocking the expression and hydrolase activity of CD73 with α,β‑methylene ADP (APCP) could counteract the protective effect of CD73 on neuronal apoptosis, while adenosine (Ado) could rescue the increased apoptosis caused by CD73 deletion. In addition, the cAMP/ protein kinase A (PKA)/cAMP response element‑binding protein (CREB) signaling pathway was also positively regulated by CD73 and Ado. In conclusion, CD73 could inhibit DRG neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Ecto‑5'‑nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway

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