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10.1681/ASN.2013101128

http://scihub22266oqcxt.onion/10.1681/ASN.2013101128
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suck abstract from ncbi


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pmid24854264
      J+Am+Soc+Nephrol 2014 ; 25 (12 ): 2778-88
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  • Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids #MMPMID24854264
  • Herzog R ; Bender TO ; Vychytil A ; Bialas K ; Aufricht C ; Kratochwill K
  • J Am Soc Nephrol 2014[Dec]; 25 (12 ): 2778-88 PMID24854264 show ga
  • The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD.
  • |Acetylglucosamine/*chemistry [MESH]
  • |Cell Survival [MESH]
  • |Cells, Cultured [MESH]
  • |Dialysis Solutions/*chemistry/pharmacology [MESH]
  • |Dipeptides/chemistry [MESH]
  • |Epithelium/*pathology [MESH]
  • |Glucose/chemistry [MESH]
  • |Glutamine/chemistry [MESH]
  • |Glycosylation [MESH]
  • |HSP72 Heat-Shock Proteins/chemistry [MESH]
  • |Humans [MESH]
  • |Microscopy, Fluorescence [MESH]
  • |Omentum/cytology [MESH]
  • |Peritoneal Dialysis/*methods [MESH]
  • |Peritoneum/pathology [MESH]
  • |Protein Processing, Post-Translational [MESH]


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