The role of Omi/HtrA2 protease in neonatal postasphyxial serum-induced apoptosis in human kidney proximal tubule cells

• Main Authors: Zhang Yong, Dong Wen-Bin, Li Qing-Ping, Deng Chun-Liang, Xiong Tao, Lei Xiao-Ping, Guo Lin
• Format: Article
• Language: English
• Published: University of Belgrade, University of Novi Sad 2012-01-01
• Series: Archives of Biological Sciences
• Subjects: Asphyxia; serum; apoptosis; Omi/HtrA2; renal injury
• Online Access: http://www.doiserbia.nb.rs/img/doi/0354-4664/2012/0354-46641204505Z.pdf

Omi/HtrA2, a proapoptotic mitochondrial serine protease, is involved in both caspase-dependent and caspaseindependent apoptosis. A growing body of evidence indicates that Omi/HtrA2 plays an important role in the pathogenesis of a variety of ischemia/reperfusion (I/R) injuries. However, the role of Omi/HtrA2 in the renal injuries that occur in neonates with asphyxia remains unknown. The present study was designed to investigate whether Omi/HtrA2 plays an important role in the types of renal injuries that are induced by neonatal postasphyxial serum. Human renal proximal tubular cell line (HK-2) cells were used as targets. A 20% serum taken from neonates one day after asphyxia was applied to the target cells as an attacking factor. We initially included control and postasphyxial-serum-attacked groups and later included a ucf-101 group in the study. In the postasphyxial-serum-treated group, cytosolic Omi/HtrA2 and caspase-3 expression in the HK-2 cells was significantly higher than in the control group. Moreover, the concentration of cytosolic caspase-3 was found to be markedly decreased in HK-2 cells in the ucf-101 group. Our results suggest both that postasphyxial serum has a potent apoptosis-inducing effect on HK-2 cells and that this effect can be partially blocked by ucf-101. Taken together, our results demonstrate for the first time that postasphyxial serum from neonates results in Omi/HtrA2 translocation from the mitochondria to the cytosol, where it promotes HK-2 cell apoptosis via a protease activity-dependent, caspasemediated pathway.