dc.creator | Eleftheriadis T., Pissas G., Filippidis G., Liakopoulos V., Stefanidis I. | en |
dc.date.accessioned | 2023-01-31T07:37:15Z | |
dc.date.available | 2023-01-31T07:37:15Z | |
dc.date.issued | 2021 | |
dc.identifier | 10.3390/biom11101522 | |
dc.identifier.issn | 2218273X | |
dc.identifier.uri | http://hdl.handle.net/11615/71332 | |
dc.description.abstract | Ischemia-reperfusion injury is the commonest form of acute kidney injury (AKI). Tubular epithelial cell senescence contributes to incomplete recovery from AKI and predisposes to subsequent chronic kidney disease. In cultures of primary proximal renal tubular epithelial cells (RPTECs) subjected to anoxia or reoxygenation, we evaluated the role of indoleamine 2,3-dioxygenase 1 (IDO) in cellular senescence. Proteins of interest were assessed with Western blotting or enzymelinked immunosorbent assay or histochemically. Under anoxia or reoxygenation, IDO expression and activity were increased. Moreover, the two IDO-derived pathways, the general control nonderepressible 2 kinase (GCN2K) pathway and the aryl-hydrocarbon receptor (AhR) pathway, were also activated. A DNA damage response (DDR) took place and led to increased levels of the cellcycle inhibitors p21 and p16, and senescence-associated β-galactosidase (SA-β-Gal) activity. Cell proliferation was inhibited, and more IL-6 was produced. The IDO inhibitor 1-DL-methyl-tryptophan ameliorated the DDR; decreased p21, p16, and SA-β-Gal activity; restored cell proliferation; and decreased IL-6 production. The AhR inhibitor CH223191 did not affect the above parameters. In conclusion, anoxia and the subsequent reoxygenation upregulate IDO. IDO depletes tryptophan and activates GCN2K. The latter enhances the anoxia-or reoxygenation-induced DDR, resulting in increased p21 and p16 expression and eventually leading to RPTEC senescence. Since cellular senescence affects AKI outcome, the role of IDO in cellular senescence and the possible therapeutic role of IDO inhibitors deserve further investigation. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | en |
dc.language.iso | en | en |
dc.source | Biomolecules | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85117148053&doi=10.3390%2fbiom11101522&partnerID=40&md5=1d877fc9b02ba0b9b6885100349c1a52 | |
dc.subject | 2524 | en |
dc.subject | ab75836 | en |
dc.subject | aromatic hydrocarbon receptor | en |
dc.subject | beta galactosidase | en |
dc.subject | cyclin dependent kinase inhibitor 1A | en |
dc.subject | cyclin dependent kinase inhibitor 2A | en |
dc.subject | indoleamine 2,3 dioxygenase | en |
dc.subject | indoleamine 2,3 dioxygenase inhibitor | en |
dc.subject | interleukin 6 | en |
dc.subject | Ki 67 antigen | en |
dc.subject | kynurenine | en |
dc.subject | nbp222112 | en |
dc.subject | phosphate buffered saline | en |
dc.subject | protein p53 | en |
dc.subject | sc25809 | en |
dc.subject | sc374609 | en |
dc.subject | 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide | en |
dc.subject | alpha-methyltryptophan | en |
dc.subject | aromatic hydrocarbon receptor | en |
dc.subject | azo compound | en |
dc.subject | cyclin dependent kinase inhibitor 2A | en |
dc.subject | EIF2AK4 protein, human | en |
dc.subject | enzyme inhibitor | en |
dc.subject | indoleamine 2,3 dioxygenase | en |
dc.subject | interleukin 6 | en |
dc.subject | oxygen | en |
dc.subject | pyrazole derivative | en |
dc.subject | Rho guanine nucleotide binding protein | en |
dc.subject | tryptophan | en |
dc.subject | acute kidney failure | en |
dc.subject | animal cell | en |
dc.subject | anoxia | en |
dc.subject | Article | en |
dc.subject | cell aging | en |
dc.subject | cell proliferation | en |
dc.subject | chronic kidney failure | en |
dc.subject | controlled study | en |
dc.subject | DNA damage response | en |
dc.subject | enzyme linked immunosorbent assay | en |
dc.subject | gene expression | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | immunoadsorption | en |
dc.subject | immunocytochemistry | en |
dc.subject | nonhuman | en |
dc.subject | protein expression | en |
dc.subject | reoxygenation | en |
dc.subject | reperfusion injury | en |
dc.subject | signal transduction | en |
dc.subject | upregulation | en |
dc.subject | Western blotting | en |
dc.subject | acute kidney failure | en |
dc.subject | animal | en |
dc.subject | cell aging | en |
dc.subject | DNA damage | en |
dc.subject | drug effect | en |
dc.subject | epithelium cell | en |
dc.subject | genetics | en |
dc.subject | hypoxia | en |
dc.subject | kidney proximal tubule | en |
dc.subject | metabolism | en |
dc.subject | mouse | en |
dc.subject | pathology | en |
dc.subject | reperfusion injury | en |
dc.subject | Acute Kidney Injury | en |
dc.subject | Animals | en |
dc.subject | Azo Compounds | en |
dc.subject | Cell Proliferation | en |
dc.subject | Cellular Senescence | en |
dc.subject | Cyclin-Dependent Kinase Inhibitor p16 | en |
dc.subject | DNA Damage | en |
dc.subject | Enzyme Inhibitors | en |
dc.subject | Epithelial Cells | en |
dc.subject | Humans | en |
dc.subject | Hypoxia | en |
dc.subject | Indoleamine-Pyrrole 2,3,-Dioxygenase | en |
dc.subject | Interleukin-6 | en |
dc.subject | Kidney Tubules, Proximal | en |
dc.subject | Mice | en |
dc.subject | Oxygen | en |
dc.subject | Protein Serine-Threonine Kinases | en |
dc.subject | Pyrazoles | en |
dc.subject | Receptors, Aryl Hydrocarbon | en |
dc.subject | Reperfusion Injury | en |
dc.subject | rho GTP-Binding Proteins | en |
dc.subject | Tryptophan | en |
dc.subject | MDPI | en |
dc.title | The role of indoleamine 2,3-dioxygenase in renal tubular epithelial cells senescence under anoxia or reoxygenation | en |
dc.type | journalArticle | en |