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

Comparative biology may reveal novel therapeuticstrategies against human diseases. Ischemia‑reperfusion (IR)injury induces a number of diseases. It is known thathibernating mammals survive IR since during hibernation,prolonged periods of torpor with a marked decrease in bloodflow and breathing rate are interrupted by short periods ofarousal. In the present study, the differences in the character‑istics of endoplasmic reticulum (ER) stress and the subsequentunfolded protein response, which are induced by IR and maycause cell death among humans, mice or the native hibernatorSyrian hamster were examined in vitro using renal proximaltubular epithelial cells (RPTECs) derived from these threesources. 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 phos‑phorylated protein kinase RNA‑like ER kinase, ubiquitinatedproteins and Bcl‑2‑associated X protein (Bax) by western blotanalysis. For proteasomal activity, a specific assay was used.The results revealed that anoxia induced ER stress in all theevaluated RPTECs, from which only the hamster‑derivedRPTECs recovered during reoxygenation. Anoxia and reoxy‑genation increased protein ubiquitination in the human‑ andmouse‑derived RPTECs, whereas this was decreased in thehamster‑derived RPTECs. Anoxia enhanced proteasomalactivity in all the evaluated RPTECs. In the human‑ andmouse‑derived RPTECs, reoxygenation reduced proteasomalactivity, which remained high in the hamster‑derived RPTECs.Anoxia and reoxygenation increased Bax expression andinduced cell death in the human‑ and mouse‑derived RPTECs,while neither Bax overexpression nor cell death occurred inthe hamster‑derived RPTECs. Thus, on the whole, the find‑ings of this study demonstrate that compared to human‑ ormouse‑derived RPTECs, those derived from the hamsterrecover more rapidly from ER stress following warmanoxia‑reoxygenation, possibly due to increased proteasomalfunction.