dc.creator | Eleftheriadis T., Pissas G., Antoniadi G., Nikolaou E., Golfinopoulos S., Liakopoulos V., Stefanidis I. | en |
dc.date.accessioned | 2023-01-31T07:37:14Z | |
dc.date.available | 2023-01-31T07:37:14Z | |
dc.date.issued | 2019 | |
dc.identifier | 10.3390/biom9120832 | |
dc.identifier.issn | 2218273X | |
dc.identifier.uri | http://hdl.handle.net/11615/71324 | |
dc.description.abstract | Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles’ heel of PD method. Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells. We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity. These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal). Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8). Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein. High-glucose conditions increased glucose transporters, glucose influx, ROS, all the high-glucose-induced harmful pathways, TGF-β1 and IL-8, cell apoptosis, and MMT. Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT. Whether such a strategy could be applied in the clinic to avoid ultrafiltration failure in PD patients remains to be investigated. © 2019 by the authors. | en |
dc.language.iso | en | en |
dc.source | Biomolecules | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076323810&doi=10.3390%2fbiom9120832&partnerID=40&md5=961a1e522798cf2cf1aa7a841a6f4f66 | |
dc.subject | actin alpha 2 | en |
dc.subject | advanced glycation end product | en |
dc.subject | caspase 3 | en |
dc.subject | general control nonderepressible 2 | en |
dc.subject | glucose | en |
dc.subject | glucose transporter 1 | en |
dc.subject | glucose transporter 3 | en |
dc.subject | glucose transporter 4 | en |
dc.subject | glyceraldehyde 3 phosphate dehydrogenase | en |
dc.subject | halofuginone | en |
dc.subject | hexosamine | en |
dc.subject | iditol dehydrogenase | en |
dc.subject | interleukin 8 | en |
dc.subject | isomerase | en |
dc.subject | lactate dehydrogenase | en |
dc.subject | methylglyoxal | en |
dc.subject | n acetylglucosamine | en |
dc.subject | protein kinase C alpha | en |
dc.subject | protein serine threonine kinase | en |
dc.subject | reactive oxygen metabolite | en |
dc.subject | sodium glucose cotransporter 1 | en |
dc.subject | transforming growth factor beta1 | en |
dc.subject | tryptophanol | en |
dc.subject | unclassified drug | en |
dc.subject | dialysis fluid | en |
dc.subject | EIF2AK4 protein, human | en |
dc.subject | glucose | en |
dc.subject | piperidine derivative | en |
dc.subject | protein serine threonine kinase | en |
dc.subject | quinazolinone derivative | en |
dc.subject | reactive oxygen metabolite | en |
dc.subject | tryptophan | en |
dc.subject | animal cell | en |
dc.subject | animal experiment | en |
dc.subject | animal model | en |
dc.subject | animal tissue | en |
dc.subject | apoptosis | en |
dc.subject | Article | en |
dc.subject | cell culture | en |
dc.subject | cell growth | en |
dc.subject | clinical assessment | en |
dc.subject | comparative study | en |
dc.subject | controlled study | en |
dc.subject | cytotoxicity | en |
dc.subject | dialysis | en |
dc.subject | drug mechanism | en |
dc.subject | enzyme linked immunosorbent assay | en |
dc.subject | epithelial mesenchymal transition | en |
dc.subject | glucose intake | en |
dc.subject | glucotoxicity | en |
dc.subject | glycation | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | kinase activity | en |
dc.subject | lipogenesis | en |
dc.subject | mesothelium cell | en |
dc.subject | mouse | en |
dc.subject | myofibroblast | en |
dc.subject | nonhuman | en |
dc.subject | peritoneal dialysis | en |
dc.subject | protein expression | en |
dc.subject | signal intensity | en |
dc.subject | ultrafiltration | en |
dc.subject | upregulation | en |
dc.subject | Western blotting | en |
dc.subject | chemistry | en |
dc.subject | cytology | en |
dc.subject | drug effect | en |
dc.subject | epithelial mesenchymal transition | en |
dc.subject | epithelium cell | en |
dc.subject | metabolism | en |
dc.subject | peritoneum | en |
dc.subject | primary cell culture | en |
dc.subject | Cells, Cultured | en |
dc.subject | Dialysis Solutions | en |
dc.subject | Epithelial Cells | en |
dc.subject | Epithelial-Mesenchymal Transition | en |
dc.subject | Glucose | en |
dc.subject | Humans | en |
dc.subject | Peritoneal Dialysis | en |
dc.subject | Peritoneum | en |
dc.subject | Piperidines | en |
dc.subject | Primary Cell Culture | en |
dc.subject | Protein-Serine-Threonine Kinases | en |
dc.subject | Quinazolinones | en |
dc.subject | Reactive Oxygen Species | en |
dc.subject | Tryptophan | en |
dc.subject | MDPI AG | en |
dc.title | Activation of general control nonderepressible-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents mesothelial to mesenchymal transition | en |
dc.type | journalArticle | en |