| Autor: |
Yasushi Ishii, Aya Fukui-Miyazaki, Sari Iwasaki, Takahiro Tsuji, Kiyohiko Hotta, Hajime Sasaki, Shimpei Nakagawa, Takuma Yoshida, Eri Murata, Koji Taniguchi, Nobuo Shinohara, Akihiro Ishizu, Masanori Kasahara, Utano Tomaru |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Experimental and Molecular Pathology, Vol 140, Iss , Pp 104939- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1096-0945 |
| DOI: |
10.1016/j.yexmp.2024.104939 |
| Popis: |
Oxidative stress caused by reactive oxygen species (ROS) is involved in the pathogenesis of renal ischemia-reperfusion injury (I/R injury), a major cause of acute kidney injury and delayed graft function (DGF). DGF is an early transplant complication that worsens graft prognosis and patient survival, but the underlying molecular changes are unclear. The proteasome is a multicatalytic enzyme complex that degrades both normal and damaged proteins, and recent studies have revealed that the immunoproteasome, a specific proteasome isoform whose proteolytic activity enhances the generation of antigenic peptides, plays critical roles in the cellular response against oxidative stress. In this study, we demonstrate the impact of the immunoproteasome in human DGF and in a mouse model of I/R injury. In patients with DGF, the expression of β5i, a specific immunoproteasome subunit, was decreased in vascular endothelial cells. In a mouse model, β5i knockout (KO) exacerbated renal I/R injury. KO mice showed greater inflammation, oxidative stress, and endothelial damage compared with wild-type mice. Impaired immunoproteasomal activity also caused increased cell death, ROS production, and expression of inflammatory factors in mouse renal vascular endothelial cells under conditions of hypoxia and reoxygenation. In conclusion, reduced expression of the immunoproteasomal catalytic subunit β5i exacerbates renal I/R injury in vivo, potentially increasing the risk of DGF. Further research targeting β5i expression in DGF could lead to the development of novel therapeutic strategies and biomarkers. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full Text from ScienceDirect