biostudies-literatureEskla KLEstonian Research FoundationEstonian Research CouncilBaltic Research Programme of the European Economic Area (EEA)European Regional Development Fundthe European Union through the European Regional Development Fund10108https://www.ebi.ac.uk/biostudies/studies/S-EPMC9456258biostudies-literatureUnknown23(17)Ischemia reperfusion injury is common in transplantation. Previous studies have shown that cooling can protect against hypoxic injury. To date, the protective effects of hypothermia have been largely associated with metabolic suppression. Since kidney transplantation is one of the most common organ transplant surgeries, we used human-derived renal proximal tubular cells (HKC8 cell line) as a model of normal renal cells. We performed a temperature titration curve from 37 °C to 22 °C and evaluated cellular respiration and molecular mechanisms that can counteract the build-up of reducing equivalents in hypoxic conditions. We show that the protective effects of hypothermia are likely to stem both from metabolic suppression (inhibitory component) and augmentation of stress tolerance (activatingInternational journal of molecular sciencesHypothermia Alleviates Reductive Stress, a Root Cause of Ischemia Reperfusion Injury.PMC9456258EEZ/BPP/VIAA/2021/82014-2020.4.01.15-0012PRG685PUT1077Ramma HVellama HVolke VEichelmann HPorosk RTarve LPeet NLaisk ALuuk HJagomae TOja VEskla KLVasar EfalseHypothermia Alleviates Reductive Stress, a Root Cause of Ischemia Reperfusion Injury.Ischemia reperfusion injury is common in transplantation. Previous studies have shown that cooling can protect against hypoxic injury. To date, the protective effects of hypothermia have been largely associated with metabolic suppression. Since kidney transplantation is one of the most common organ transplant surgeries, we used human-derived renal proximal tubular cells (HKC8 cell line) as a model of normal renal cells. We performed a temperature titration curve from 37 °C to 22 °C and evaluated cellular respiration and molecular mechanisms that can counteract the build-up of reducing equivalents in hypoxic conditions. We show that the protective effects of hypothermia are likely to stem both from metabolic suppression (inhibitory component) and augmentation of stress tolerance (activating2022-01-01T00:00:00Z2022 Sep2025-08-30T03:13:10.218Z2025-08-30T03:09:24.914ZS-EPMC94562583607750410.3390/ijms231710108