Targeted Restoration of GPX3 Attenuates Renal Ischemia/Reperfusion Injury by Balancing Selenoprotein Expression and Inhibiting ROS-mediated Mitochondrial Apoptosis

Yikun Wu ^1,2, Hua Shi ³, Yuangao Xu ⁴

⁰Guizhou University Medical College, Guiyang, China.

Transplantation +

|

May 21, 2024

View abstract on PubMed

Summary

Restoring glutathione peroxidase 3 (GPX3) can protect against kidney injury from ischemia/reperfusion (IR). GPX3 balances selenoprotein expression and reduces apoptosis, suggesting it as a therapeutic target for renal IR injury.

Area Of Science

Nephrology
Molecular Biology
Biochemistry

Background

Renal ischemia/reperfusion (IR) injury is a primary cause of acute kidney injury.
Reduced levels of glutathione peroxidase 3 (GPX3) are linked to renal IR injury.
The precise mechanism for restoring GPX3 in renal IR injury requires elucidation.

Purpose Of The Study

To investigate the role and mechanism of glutathione peroxidase 3 (GPX3) in renal ischemia/reperfusion (IR) injury.
To determine if GPX3 can be therapeutically targeted to mitigate renal IR injury.

Main Methods

Assessed GPX3 distribution and levels in renal IR injury models.
Utilized adeno-associated virus 9 to overexpress GPX3 in vivo and in vitro.
Employed reverse molecular docking to identify ebselen as a potential interacting molecule with GPX3.

Main Results

GPX3 is abundant in kidneys and downregulated during IR injury.
GPX3 overexpression mitigated renal IR injury and protected tubular cells from apoptosis.
GPX3 normalized selenoprotein expression and inhibited reactive oxygen species-induced mitochondrial apoptosis.

Conclusions

Targeted restoration of GPX3 attenuates renal IR injury.
GPX3 acts by balancing selenoprotein expression and inhibiting mitochondrial apoptosis.
GPX3 represents a promising therapeutic target for managing renal IR injury.