Open Access

Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells

  • Authors:
    • Theodoros Eleftheriadis
    • Georgios Pissas
    • Spyridon Golfinopoulos
    • Vassilios Liakopoulos
    • Ioannis Stefanidis
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  • Published online on: April 21, 2021     https://doi.org/10.3892/mmr.2021.12111
  • Article Number: 472
  • Copyright: © Eleftheriadis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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June-2021
Volume 23 Issue 6

Print ISSN: 1791-2997
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Spandidos Publications style
Eleftheriadis T, Pissas G, Golfinopoulos S, Liakopoulos V and Stefanidis I: Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells. Mol Med Rep 23: 472, 2021
APA
Eleftheriadis, T., Pissas, G., Golfinopoulos, S., Liakopoulos, V., & Stefanidis, I. (2021). Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells. Molecular Medicine Reports, 23, 472. https://doi.org/10.3892/mmr.2021.12111
MLA
Eleftheriadis, T., Pissas, G., Golfinopoulos, S., Liakopoulos, V., Stefanidis, I."Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells". Molecular Medicine Reports 23.6 (2021): 472.
Chicago
Eleftheriadis, T., Pissas, G., Golfinopoulos, S., Liakopoulos, V., Stefanidis, I."Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells". Molecular Medicine Reports 23, no. 6 (2021): 472. https://doi.org/10.3892/mmr.2021.12111