2. Academic Validation
  3. PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage

PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage

  • J Integr Neurosci. 2023 Nov 23;22(6):168. doi: 10.31083/j.jin2206168.
Xiao-Yi Xiong 1 2 3,  Yan-Jing Liang 1,  Xin-Xiao Zhang 1,  Su-Hao Yang 1,  Zhan-Qiong Zhong 4,  Shu-Qing Liu 1,  Jia-Yi Sun 5,  Yong Tang 2 3 6 7,  Shu-Guang Yu 1 2 3
Affiliations

Affiliations

  • 1 Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine; 611137 Chengdu, Sichuan, China.
  • 2 Sichuan Provincial Key Laboratory for Acupuncture & Chronobiology, 611137 Chengdu, Sichuan, China.
  • 3 Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, 611137 Chengdu, Sichuan, China.
  • 4 School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, 611137 Chengdu, Sichuan, China.
  • 5 Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, 611137 Chengdu, Sichuan, China.
  • 6 International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, 611137 Chengdu, Sichuan, China.
  • 7 School of Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, 611137 Chengdu, Sichuan, China.
PMID: 38176945 DOI: 10.31083/j.jin2206168
Abstract

Background: The purpose of this study was to investigate the potential involvement of Pyruvate Kinase M2 (PKM2), an enzyme acting as a rate-limiting enzyme in the final phase of glycolysis, in the regulation of glial activation and brain damage of intracerebral hemorrhage (ICH).

Methods: Western blotting and immunofluorescence were performed to investigate PKM2 expression, terminal deoxynucleotidyl transferase deoxyurinary triphosphate (dUTP) nick end labeling staining, hematoxylin and eosin staining, and behavioral tests were employed to evaluate the brain damage of ICH mice, and RNA-seq and bioinformatic analyses were performed to detect gene expression changes in ICH mice treated with TEPP-46.

Results: Increased PKM2 levels in perihematomal brain tissue were found starting from 3 days following ICH and peaked at 5 and 7 days post ICH. The increased expression of PKM2 was mainly co-localized with glial fibrillary acidic protein (GFAP)+ astrocytes and ionized calcium binding adaptor molecule-1 (IBA-1)+ microglia. Furthermore, we observed a notable increase in the nuclear translocation of PKM2 in glial cells following ICH. TEPP-46 treatment significantly reduced PKM2 nuclear translocation, and effectively attenuated glial activation and brain injury, and improved functional recovery of mice with ICH. RNA-seq data indicated that 91.1% (205/225) of differentially expressed genes (DEGs) were down-regulated in the TEPP-46 treated groups compared with the vehicle-treated groups in ICH brains. Furthermore, bioinformatic analyses revealed that these down-regulated DEGs were involved in a variety of biological processes, including Autophagy and metabolic processes. In addition, the majority of these downregulated DEGs had a primary high expression in neurons, with subsequent expression seen in endothelial cells, microglia, and astrocytes.

Conclusions: These results indicate that increased PKM2 nuclear translocation promotes the activation of glial cells after ICH, hence aggravating ICH-induced brain damage, and aggravates the brain injury induced by ICH. This highlights a potential therapeutic target for inhibiting glial activation to attenuate brain injury after ICH.

Keywords

PKM2; brain injury; glial cell; intracerebral hemorrhage.

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