Title
Omi/Htra2 Protease Mediates Cisplatin-Induced Cell Death In Renal Cells
Keywords
Apoptosis; Mitochondrial protein; Proximal tubular cells; Serine protease; Ucf-101
Abstract
Omi/HtrA2 is a mitochondrial proapoptotic serine protease that is able to induce both caspase-dependent and caspase-independent cell death. After apoptotic stimuli, Omi is released to the cytoplasm where it binds and cleaves inhibitor of apoptosis proteins. In this report, we investigated the role of Omi in renal cell death following cisplatin treatment. Using primary mouse proximal tubule cells, as well as established renal cell lines, we show that the level of Omi protein is upregulated after treatment with cisplatin. This upregulation is followed by the release of Omi from mitochondria to the cytoplasm and degradation of XIAP. Reducing the endogenous level of Omi protein using RNA interference renders renal cells resistant to cisplatin-induced cell death. Furthermore, we show that the proteolytic activity of Omi is necessary and essential for cisplatin-induced cell death in this system. When renal cells are treated with Omi's specific inhibitor, ucf-101, they become significantly resistant, to cisplatin-induced cell death. Ucf-101 was also able to minimize cisplatin-induced nephrotoxic injury in animals. Our results demonstrate that Omi is a major mediator of cisplatin-induced cell death in renal cells and suggest a way to limit renal injury by specifically inhibiting its proteolytic activity.
Publication Date
2-1-2005
Publication Title
American Journal of Physiology - Renal Physiology
Volume
288
Issue
2 57-2
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1152/ajprenal.00154.2004
Copyright Status
Unknown
Socpus ID
19944427658 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/19944427658
STARS Citation
Cilenti, Lucia; Kyriazis, George A.; and Soundarapandian, Mangala M., "Omi/Htra2 Protease Mediates Cisplatin-Induced Cell Death In Renal Cells" (2005). Scopus Export 2000s. 4115.
https://stars.library.ucf.edu/scopus2000/4115