Heliox alleviates ischemia-reperfusion-induced damage to neuronal cells by repressing the USP46-SNX5 Axis-triggered ferroptosis

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-02-03 DOI:10.1016/j.expneurol.2025.115175

Hualing Yang , Zhanxiang Wang , Wei Xiong , Liying Zhou , Shuai Yu

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引用次数: 0

Abstract

Background

Cerebral ischemia-reperfusion (I/R) causes brain cell dysfunction and death. Heliox treatment shows therapeutic benefits in treating certain respiratory conditions. Here, we explore the mechanism by which heliox alleviates ferroptosis of neuronal cells injured by I/R treatment.

Method

OGD/R-treated SH-SY5Y cells were used and screened for USPs whose expression is induced by OGD/R but suppressed by heliox treatment. Mass spectrometry was conducted to identify proteins that interact with USP46. The impact of SNX5 deficiency on the ferroptosis of USP46-overexpressing neuronal cells following sequential OGD/R and heliox treatment was also explored. Finally, the effect of USP46 overexpression on brain cell ferroptosis in a cerebral I/R rat model was explored.

Results

Deubiquitinase USP46 is targeted by heliox treatment in neuronal cells. USP46 expression is stimulated by I/R, and its overexpression enhances ferroptosis in I/R-treated neuronal cells. USP46 interacts with and deubiquitinates SNX5, a ferroptosis promoter, thereby increasing its stability. The knockdown of SNX5 abolishes the ferroptosis-promoting effect of USP46 in I/R-treated neuronal cells. Excessive USP46 attenuates the protective effect of heliox treatment on I/R-triggered cerebral damage in a rat model.

Conclusion

These observations highlight the ferroptosis-promoting function of the USP46-SNX5 axis in I/R-treated neuronal cells.

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.