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Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis

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Abstract

Background

Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation.

Methods and results

Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II’s neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis.

Conclusions

Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.

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Data availability

The data generated in our study are available upon request from the corresponding author.

Abbreviations

ICH:

Intracerebral hemorrhage

Prx II:

Peroxiredoxin II

ROS:

Reactive oxygen species

ER:

Endoplasmic reticulum

LPS:

Lipopolysaccharide

HT22:

Hippocampal neuron cells

OD:

Optical density

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Acknowledgements

This work was supported by Heilongjiang Provincial Natural Science Foundation of China (LH2023C076). This research was supported by the National Research Council of Science & Technology (NST) grant by the Korea government (MSIT) (No. CCL23041-100, KRIBB-NTM2562311).

Funding

This research was supported by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM5162423).

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Author notes

  1. Mei-Hua Jin and Xiao-Dong Liu these authors are contributed equally to this work.

Authors and Affiliations

  1. College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China

    Mei-Hua Jin, Xiao-Dong Liu, Hu-Nan Sun & Ying-Hao Han

  2. Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeonbuk, 56216, Republic of Korea

    Taeho Kwon

  3. Department of Applied Biological Engineering, KRIBB School of Biotechnology, Korea National University of Science and Technology (UST), Daejeon, 34113, Republic of Korea

    Taeho Kwon

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Contributions

MHJ, XDL contributed to the conception of the study. YHH and TK contributed to the execution of the experiment and data analysis. MHJ, XDL, HYX, TK, HNS and YHH performed the analysis and the quality assessment of the study. MHJ, XDL, YHH, and TK were responsible for the study design, writing the manuscript, and performing the literature search. All authors read and approved the final manuscript.

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Correspondence to Ying-Hao Han or Taeho Kwon.

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Jin, MH., Liu, XD., Sun, HN. et al. Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis. Mol Biol Rep 51, 607 (2024). https://doi.org/10.1007/s11033-024-09568-5

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