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The Temporal and Spatial Changes of Autophagy and PI3K Isoforms in Different Neural Cells After Hypoxia/Reoxygenation Injury

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Abstract

There are limited therapeutic options for patient with traumatic spinal cord injury (SCI). Phosphoinositide 3-kinase family (PI3Ks) are the key molecules for regulating cell autophagy, which is a possible way of treating SCI. As we know, PI3K family are composed of eight isoforms, which are distributed into three classes. While the role of PI3Ks in regulating autophagy is controversial and the effects may be in a cell-specific manner. Different isoforms do not distribute in neural cells consistently and it is not clear how the PI3K isoforms regulate and interact with autophagy. Therefore, we explored the distributions and expression of different PI3K isoforms in two key neural cells (PC12 cells and astrocytes). The results showed that the expression of LC3II/I and p62, which are the markers of autophagy, changed in different patterns in PC12 cells and astrocytes after hypoxia/reoxygenation injury (H/R). Furthermore, the mRNA level of eight PI3K isoforms did not change in the same way, and even for the same isoform the mRNA activities are different between PC12 cells and astrocytes. What is more, the results of western blot of PI3K isoforms after H/R were inconsistent with the relevant mRNA. Based on this study, the therapeutic effects of regulating autophagy on SCI are not confirmed definitely, and its molecular mechanisms may be related with different temporal and spatial patterns of activation and distributions of PI3K isoforms.

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Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank Beijing LabWecome Technology Co., Ltd. for technical support.

Funding

This work study was partially supported by the Beijing Excellent Talent Training Funding (grant no. 2017000021469G215), the Natural Science Foundation of Capital Medical University of China (grant nos. PYZ2017082; PYZ2018081), the National Key Research and Development Program of China (grant no. 2018YFF0301103), and the High Level Public Health Technology Talent Construction Project (grant nos. Leading Talent-02-05).

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  1. Department of Orthopedics, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China

    Duo Zhang, Baoge Liu, Wei Cui, Di Zhu, Jichao Zhu, Shuo Duan & Chenxi Li

  2. Department of Orthopedics, Capital Medical University Electric Power Hospital, Beijing, 100073, China

    Xuanyu Chen

  3. Department of Spinal Cord Injury Rehabilitation, China Rehabilitation Research Center, Beijing, 100068, China

    Yuan Yuan

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Duo Zhang and Baoge Liu conceived and designed the study. Duo Zhang and Xuanyu Chen participated the cell experiments. Duo Zhang, Wei Cui, Yuan Yuan integrated and analyzed the experimental data. Duo Zhang drafted the manuscript. Di Zhu, Jichao Zhu, Shuo Duan, and Chenxi Li contributed the statistical analysis. Baoge Liu and Duo Zhang confirmed the authenticity of all the raw data. All authors have read and approved the final manuscript.

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Zhang, D., Chen, X., Liu, B. et al. The Temporal and Spatial Changes of Autophagy and PI3K Isoforms in Different Neural Cells After Hypoxia/Reoxygenation Injury. Mol Neurobiol 60, 5366–5377 (2023). https://doi.org/10.1007/s12035-023-03421-9

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