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Integrated Proteome and Phosphoproteome Analyses Reveal Early- and Late-Stage Protein Networks of Traumatic Brain Injury

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Abstract

Traumatic brain injury (TBI) is a major public health concern all around the world. Accumulating evidence suggests that pathological processes after brain injury continuously evolve. Here, we identified the differentially expressed proteins (DEPs) and differentially expressed phosphoproteins (DEPPs) in the early and late stages of TBI in mice using TMT labeling, enrichment of Phos affinity followed, and high-resolution LC-MS/MS analysis. Subsequently, integrative analyses, including functional enrichment-based clustering analysis, motif analysis, cross-talk pathway/process enrichment analysis, and protein-protein interaction enrichment analysis were performed to further identify the different and similar pathophysiologic mechanisms in the early and late stage. Our work reveals a map of early and late-stage protein networks in TBI, which shed light on useful biomarkers and the underlying mechanisms in TBI and its sequelae.

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Abbreviations

TBI:

Traumatic brain injury

DEPs:

Differentially expressed proteins

DEPPs:

differentially expressed phosphoproteins

Group 1d/C:

Group 1d when compared to the sham group

Group 7d/C:

Group 7d when compared to the sham group

Group 7d/1d:

Group 7d when compared to group 1d

NSS:

Neurological severity score

S:

Serine

T:

Threonine

Y:

Tyrosine

D:

Asparticacid

E:

Glutamicacid

K:

Lysine

R:

Arginine

P:

Proline

V:

Valine

IGF:

Insulin-like growth factor

GH:

Growth hormone

CCI:

Cortical controlled impact

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Acknowledgements

We thank members of the Institute of Neurosurgery for their input and stimulating discussions, and many other colleagues of the Department of Neurosurgery for helpful comments on this manuscript. We thank PTM-Biolabs Co., Ltd, Hangzhou, China, for technical assistance in this work.

Funding

This research was funded by the National Natural Science Foundation of China (Grant No. 81771322, 82171363, 82171321, 81871023), the Youth Talent Lifting Project (Grant No. 17-JCJQ-QT-037), and the Youth Nova Program of Shanxi (Grant No. 2021KJXX-19).

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Authors and Affiliations

  1. Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Yutao Huang, Haofuzi Zhang, Erwan Yang, Kangyi Yue, Xiangyu Gao, Shuhui Dai, Jialiang Wei, Yuefan Yang, Peng Luo & Xiaofan Jiang

  2. Department of Biomedical Engineering, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Yuefan Yang

  3. Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Xin Li

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  1. Yutao Huang
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  2. Haofuzi Zhang
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  4. Kangyi Yue
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  10. Xin Li
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Correspondence to Peng Luo, Xin Li or Xiaofan Jiang.

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The animal study was performed under the guidance of the National Institutes of Health Guide for the Care and Use of Laboratory Animals at the Fourth Military Medical University.

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Yutao Huang, Haofuzi Zhang, and Erwan Yang contributed equally to this work.

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Huang, Y., Zhang, H., Yang, E. et al. Integrated Proteome and Phosphoproteome Analyses Reveal Early- and Late-Stage Protein Networks of Traumatic Brain Injury. J Mol Neurosci 72, 759–771 (2022). https://doi.org/10.1007/s12031-021-01949-w

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