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WD-40 repeat protein 26 protects against oxidative stress-induced injury in astrocytes via Nrf2/HO-1 pathways

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Abstract

Background

Stroke is the leading cause of disability and the third leading cause of death in the world, and no effective treatment has been developed. Oxidative stress-induced cell injury and genomic instability is implicated in the pathogenesis of stroke, whose prognosis remains poor.

Methods

A model of cerebral ischemic/reperfusion injury model was established through four artery occlusions. This study was carried out using western blot, flow cytometry and RT-PCR on cell line U251-MG. The cytotoxic effect of H2O2 and expression of LDH, caspase-3, MDA and SOD was analyzed by assay kit.

Results

We found that the expression of WDR26 was induced in cerebral ischemia–reperfusion injury in vivo and the expression of WDR26 was induced by H2O2 in a dose- and time-dependent manner in vitro. WDR26 over-expression significantly suppressed H2O2-induced cell death and caspase-3-mediated apoptosis in U251-MG cells. In contrast, inhibition of WDR26 markedly enhanced cell death in U251-MG cells. In addition, WDR26 regulated oxidative stress response and induced Nrf2/HO-1 pathway.

Conclusions

These findings suggest that WDR26 mediates H2O2-induced oxidative stress and cell injury, possibly by reducing the intrinsic apoptotic pathway and activating Nrf2 and HO-1 in astrocytes.

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Data availability

Not applicable.

Code availability

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Abbreviations

ROS:

Reactive oxygen species

WDR26:

WD-40 repeat protein 26

GH:

Glycine-histidine

MAPK:

Mitogen-activated protein kinase

Gβγ:

G protein βγ

LDH:

Lactate dehydrogenase

DMSO:

Dimethyl sulfoxide

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

AS:

SiRNA

HO-1:

Heme oxygenase-1

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Funding

This work was supported by National Natural Science Foundation of China (Grant Nos. 82172147; 81571880; 81373147; 30901555; 30972870; 81360080) and Natural Science Foundation of Hunan Province (Grant Nos. 2021JJ30900; 2016JJ2157).

Author information

Authors and Affiliations

  1. Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China

    Ying Liu, Yao Zhao, Kexin Li & Yunfei Xu

  2. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Ying Liu, Yao Zhao, Kexin Li, Yunfei Xu & Jie Zhao

  3. Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, 410008, Hunan, China

    Ying Liu, Yao Zhao, Kexin Li, Yunfei Xu & Jie Zhao

  4. Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China

    Shuying Miao

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  1. Ying Liu
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  3. Kexin Li
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  4. Shuying Miao
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Contributions

YL and JZ designed and directed the project. YZ performed the experiments. YZ, YL, KL, YX, SM and JZ analyzed the data. All authors discussed the results and contributed to the final manuscript. YZ wrote the manuscript.

Corresponding author

Correspondence to Jie Zhao.

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The authors report no conflicts of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted by Experimental Animal Center of Central South University (Changsha, China), No: 2018sydw0222.

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Liu, Y., Zhao, Y., Li, K. et al. WD-40 repeat protein 26 protects against oxidative stress-induced injury in astrocytes via Nrf2/HO-1 pathways. Mol Biol Rep 49, 1045–1056 (2022). https://doi.org/10.1007/s11033-021-06925-6

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  • DOI: https://doi.org/10.1007/s11033-021-06925-6

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