naa a22 4500 510746268 CHVBK 20180411083047.0 cr unu---uuuuu 180411e20130901xx s 000 0 eng 10.1007/s12192-013-0410-6 doi (NATIONALLICENCE)springer-10.1007/s12192-013-0410-6 GSK-3β inhibition protects mesothelial cells during experimental peritoneal dialysis through upregulation of the heat shock response [Elektronische Daten] [K. Rusai, R. Herzog, L. Kuster, K. Kratochwill, C. Aufricht] Non-physiological components of peritoneal dialysis fluids (PDF) lead to the injury of peritoneal mesothelial cells resulting in the failure of peritoneal dialysis (PD) potentially via inadequate induction of the protective heat shock response (HSR). Glycogen synthase kinase-3β (GSK-3β) is a negative regulator of cell survival partly by suppression of the HSR and is influenced by stress stimuli also present in conventional PDF. The effects of PDF on GSK-3β activation and the impact of GSK-3β inhibition with lithium (LiCl) were investigated on cell survival with special regard to HSR, in particular to heat shock transcription factor 1 (HSF-1) activation and Hsp72 production in an in vitro model of PD using MeT-5A and primary mesothelial cells. Incubation of cells with the PDF Dianeal® (glucose-based, low pH, high glucose degradation products (GDP)) and Extraneal® (icodextrin-based, low pH, low GDP) caused activation of GSK-3β compared to the other tested PDF, i.e. Balance®, Physioneal® (normal pH, glucose-based, low GDP) and Nutrineal® (moderately acidic, amino acid-based). Inhibition of GSK-3β with LiCl in Dianeal® and Extraneal®-treated cells dose-dependently decreased cell damage and death rate and was paralleled by higher HSF-1 activation and Hsp72 expression. GSK-3β is activated by low pH GDP containing PDF with and without glucose as osmotic agent, indicating that GSK-3β is involved in mesothelial cell signalling in response to experimental PD. Inhibition of GSK-3β with LiCl ameliorated cell injury and improved HSR upon PDF exposure. Thus, GSK-3β inhibitors likely have therapeutic potential as cytoprotective additive for decreasing PDF toxicity. Cell Stress Society International, 2013 GSK-3β inhibition nationallicence Heat shock response nationallicence Lithium nationallicence Mesothelial cells nationallicence PD fluids nationallicence Rusai K. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut Herzog R. Zytoprotec GmbH, 1010, Vienna, Austria aut Kuster L. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut Kratochwill K. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut Aufricht C. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut Cell Stress and Chaperones Springer Netherlands 18/5(2013-09-01), 569-579 1355-8145 18:5<569 2013 18 12192 https://doi.org/10.1007/s12192-013-0410-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12192-013-0410-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rusai K. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Herzog R. Zytoprotec GmbH, 1010, Vienna, Austria aut NATIONALLICENCE 700 1- Kuster L. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Kratochwill K. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Aufricht C. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 773 0- Cell Stress and Chaperones Springer Netherlands 18/5(2013-09-01), 569-579 1355-8145 18:5<569 2013 18 12192 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer