Renal tubular epithelial cells of the native hibernator Syrian hamster recover more rapidly from endoplasmic reticulum stress compared to those of human or mouse following warm anoxia-reoxygenation, possibly due to increased proteasomal function

Eleftheriadis,Theodoros; Pissas,Georgios; Antoniadi,Georgia; Filippidis,Georgios; Liakopoulos,Vassilios; Stefanidis,Ioannis

doi:10.3892/wasj.2018.4

Renal tubular epithelial cells of the native hibernator Syrian hamster recover more rapidly from endoplasmic reticulum stress compared to those of human or mouse following warm anoxia-reoxygenation, possibly due to increased proteasomal function

Authors:
- Theodoros Eleftheriadis
- Georgios Pissas
- Georgia Antoniadi
- Georgios Filippidis
- Vassilios Liakopoulos
- Ioannis Stefanidis
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Affiliations: Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
Published online on: December 6, 2018 https://doi.org/10.3892/wasj.2018.4
Pages: 39-46
Copyright: © Eleftheriadis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Comparative biology may reveal novel therapeutic strategies against human diseases. Ischemia‑reperfusion (IR) injury induces a number of diseases. It is known that hibernating mammals survive IR since during hibernation, prolonged periods of torpor with a marked decrease in blood flow and breathing rate are interrupted by short periods of arousal. In the present study, the differences in the characteristics of endoplasmic reticulum (ER) stress and the subsequent unfolded protein response, which are induced by IR and may cause cell death among humans, mice or the native hibernator Syrian hamster were examined in vitro using renal proximal tubular epithelial cells (RPTECs) derived from these three sources. RPTECs were subjected to anoxia or reoxygenation, both at 37˚C. Cell death was measured by LDH release assay. ER stress was assessed by determining the levels of phosphorylated protein kinase RNA‑like ER kinase, ubiquitinated proteins and Bcl‑2‑associated X protein (Bax) by western blot analysis. For proteasomal activity, a specific assay was used. The results revealed that anoxia induced ER stress in all the evaluated RPTECs, from which only the hamster‑derived RPTECs recovered during reoxygenation. Anoxia and reoxygenation increased protein ubiquitination in the human‑ and mouse‑derived RPTECs, whereas this was decreased in the hamster‑derived RPTECs. Anoxia enhanced proteasomal activity in all the evaluated RPTECs. In the human‑ and mouse‑derived RPTECs, reoxygenation reduced proteasomal activity, which remained high in the hamster‑derived RPTECs. Anoxia and reoxygenation increased Bax expression and induced cell death in the human‑ and mouse‑derived RPTECs, while neither Bax overexpression nor cell death occurred in the hamster‑derived RPTECs. Thus, on the whole, the findings of this study demonstrate that compared to human‑ or mouse‑derived RPTECs, those derived from the hamster recover more rapidly from ER stress following warm anoxia‑reoxygenation, possibly due to increased proteasomal function.

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