Stress Responses and Conditioning Effects in Mesothelial Cells Exposed to Peritoneal Dialysis Fluid

被引:23
作者
Kratochwill, Klaus [1 ]
Lechner, Michael [2 ]
Siehs, Christian [3 ]
Lederhuber, Hans C. [1 ]
Rehulka, Pavel [4 ]
Endemann, Michaela [1 ]
Kasper, David C. [1 ]
Herkner, Kurt R. [1 ]
Mayer, Bernd [3 ]
Rizzi, Andreas [2 ]
Aufricht, Christoph [1 ]
机构
[1] Med Univ Wien, Univ Klin F Kinder & Jugenheilkunde, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria
[2] Univ Vienna, Inst Analyt Chem & Food Chem, A-1010 Vienna, Austria
[3] Emergentec Biodev GmbH, Vienna, Austria
[4] Acad Sci Czech Republ, Inst Analyt Chem, CS-61142 Brno, Czech Republic
基金
奥地利科学基金会;
关键词
HEAT-SHOCK PROTEINS; HIGH UREA CONCENTRATIONS; CIS-TRANS-ISOMERASES; MOLECULAR CHAPERONES; GENE-EXPRESSION; OSMOTIC-STRESS; IN-VITRO; PROTEOMICS; APOPTOSIS; KIDNEY;
D O I
10.1021/pr800916s
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Renal replacement therapy by peritoneal dialysis is frequently complicated by technical failure. Peritoneal dialysis fluids (PDF) cause injury to the peritoneal mesothelial cell layer due to their cytotoxicity. As only isolated elements of the involved cellular processes have been studied before, we aimed at a global assessment of the mesothelial stress response to PDF. Following single or repeated exposure to PDF or control medium, proteomics and bioinformatics techniques were combined to study effects in mesothelial cells (MeT-5A). Protein expression was assessed by two-dimensional gel electrophoresis, and significantly altered spots were identified by MALDI-TOF MS and MS2 techniques. The lists of experimentally derived candidate proteins were expanded by a next neighbor approach and analyzed for significantly enriched biological processes. To address the problem of an unknown portion of false positive spots in 2DGE, only proteins showing significant p-values on both levels were further interpreted. Single PDF exposure resulted in reduction of biological processes in favor of reparative responses, including protein metabolism, modification and folding, with chaperones as a major subgroup. The observed biological processes triggered by this acute PDF exposure mainly contained functionally interwoven multitasking proteins contributing as well to cytoskeletal reorganization and defense mechanisms. Repeated PDF exposure resulted in attenuated protein regulation, reflecting inhibition of stress responses by high levels of preincluced chaperones. The identified proteins were less attributable to acute cellular injury but rather to specialized functions with a reduced number of involved multitasking proteins. This finding agrees well with the concept of conditioning effects and cytoprotection. In conclusion, this study describes the reprogrammed proteome of mesothelial cells during recovery from PDF exposure and adaption to repetitive stress. A broad stress response with a number of highly overlapping processes and multitasking proteins shifts toward a more specific response of only few less overlapping processes.
引用
收藏
页码:1731 / 1747
页数:17
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