TY - JOUR AB - The present study evaluated indoleamine 2,3‑dioxygenase 1 (IDO) kinetics and how it affects cell survival during the two distinct phases of ischemia‑reperfusion (I‑R) injury. Primary renal proximal tubular epithelial cells (RPTECs) were cultured under anoxia or reoxygenation with or without the IDO inhibitor 1‑DL‑methyltryptophan, the aryl‑hydrocarbon receptor (AhR) inhibitor CH223191 or the ferroptosis inhibitor α‑tocopherol. Using cell imaging, colorimetric assays, PCR and western blotting, it was demonstrated that IDO was upregulated and induced apoptosis during anoxia. The related molecular pathway entails tryptophan degradation, general control non‑derepressible‑2 kinase (GCN2K) activation, increased level of phosphorylated eukaryotic translation initiation factor 2α, activating transcription factor (ATF)4, ATF3, C/EBP homologous protein, phosphorylated p53, p53, Bax, death receptor‑5 and eventually activated cleaved caspase‑3. Reoxygenation also upregulated IDO, which, in this case, induced ferroptosis. The related molecular pathway encompasses kynurenine production, AhR activation, cytochrome p450 enzymes increase, reactive oxygen species generation and eventually ferroptosis. In conclusion, in RPTECs, both anoxia and reoxygenation upregulated IDO, which in turn induced GCN2K‑mediated apoptosis and AhR‑mediated ferroptosis. Since both phases of I‑R injury share IDO upregulation as a common point, its inhibition may prove a useful therapeutic strategy for preventing or attenuating I‑R injury. AD - Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece AU - Eleftheriadis,Theodoros AU - Pissas,Georgios AU - Golfinopoulos,Spyridon AU - Liakopoulos,Vassilios AU - Stefanidis,Ioannis DA - 2021/06/01 DO - 10.3892/mmr.2021.12111 IS - 6 JO - Mol Med Rep KW - ischemia-reperfusion indoleamine 2 3-dioxygenase apoptosis ferroptosis general control non-derepressible-2 kinase aryl-hydrocarbon receptor PY - 2021 SN - 1791-2997 1791-3004 SP - 472 ST - Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells T2 - Molecular Medicine Reports TI - Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells UR - https://doi.org/10.3892/mmr.2021.12111 VL - 23 ER -