Phosphorylation of PrxII promotes JNK-dependent apoptosis in adult cloned pig kidney

Abstract Organ transplantation is the most effective medical therapy for end-stage renal disease patients; however, there is a critical shortage of human donor organs. Therefore, xenotransplantation using genetically modified cloned porcine kidney is considered as a viable solution, but its fundamental therapeutic mechanism and difference from non-cloned porcine or human kidney for its clinical application is not well known. Here, we performed proteomic analysis to investigate the differentially expressed molecules in kidney tissue obtained from cloned porcine by SCNT, when compared with normal porcine kidney in same age as a control. A total of 80 protein spots were differentially expressed between cloned porcine kidney and control kidney, including apoptotic proteins, structural and anti-oxidant related proteins. Furthermore, very interestingly, the differential expression pattern of PrxII in the cloned porcine kidney was distinguishable from that in the control kidney in terms of the pI and molecular weight. Along with this, apoptotic marker proteins were up-regulated in the cloned porcine kidney. We suggested that these alterations were induced by post-translational modification such as phosphorylation in PrxII and could be mediated by JNK. With this result, we also observed that the down-regulation of JNK activity was caused by blockage of phosphorylation in PrxII T89A region. Taken together, cloned porcine kidney is more susceptible in JNK-induced apoptosis caused by PrxII phosphorylation, in oxidative stress condition. These results will be helpful in the application of cloned porcine xeno-transplants for treating end-stage renal disease patients in a clinical setting.