Phosphorylation of PrxII promotes JNK-dependent apoptosis in adult cloned pig kidney |
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| Affiliation: | 1. Department of Oral Pharmacology, School of Dentistry, Brain Korea 21 Plus Project, Chonbuk National University, Jeonju, Republic of Korea;2. Samsung Advanced Institute of Technology, Well Aging Research Center, Suwon, Republic of Korea;3. College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea;4. Natural Medicine Research Institute, Department of Pharmacy, College of Pharmacy, Mokpo National University, Jeonnam 534-729, Republic of Korea;5. Department of Animal Science and Technology, Sunchon National University, Suncheon, Republic of Korea;1. ABRC, CMRI, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, South Korea;2. School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea;3. Department of Anatomy, College of Medicine, Kyungpook National University, Daegu, 41944, South Korea;4. Department of Biomedical Sciences, University of Ulsan, College of Medicine, Seoul, 05505, South Korea;1. School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia;2. Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA;3. Department of Medicine, Division of Rheumatology and Connective Tissue Diseases, University of Tennessee Health Science Center, Memphis, TN, USA;4. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA;5. Department of Pharmaceutical Sciences, School of Pharmacy, South College, Knoxville, TN, USA;1. College of Pharmacy, Dalian Medical University, Dalian 116044, People’s Republic of China;2. College of Basic Medical Science, Dalian Medical University, Dalian 116044, People’s Republic of China;1. Biomedical Sciences, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand;2. Departments of Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, USA;3. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand;4. Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;5. Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, MA 01003, USA;1. Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway;2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway;1. Rutgers Cancer Institute of New Jersey, Department of Medicine, Division of Medical Oncology – Rutgers, The State University of New Jersey, Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08903, USA;2. Rutgers Cancer Institute of New Jersey, Department of Surgery, Division of Surgical Oncology, Rutgers, The State University of New Jersey, Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08903, USA;3. Center for Biomedical Imaging & Informatics – Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA;4. Rutgers Cancer Institute of New Jersey – Department of Pathology and Laboratory Medicine, Robert Wood Johnson University Hospital, 1 RWJ Place, New Brunswick, NJ 08901, USA;5. Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA |
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| 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. |
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| Keywords: | Porcine SCNT Kidney Proteomics PrxII |
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