Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Hypothermia attenuates the renal injury induced by ischemia-reperfusion. However, the detailed molecular pathway remains unknown. ERK and HIF1 are known to protect against ischemia-reperfusion injury. Also, it has been reported that hypothermia may induce ERK and HIF1 in various cellular injury model. We evaluated the role played by ERK and HIF1 in hypothermic protection against renal ischemia-reperfusion injury.
*Methods: C57Bl/6 mice were divided into the following groups: sham-operated (cold, 32C) vs normal temperature (37C); ischemia-reperfusion mice (32C vs 37C); and PD98059- or vehicle-treated ischemia-reperfusion mice (32C). Kidneys were harvested 10 and 27 minutes after induction of renal ischemia and 24 hours after ischemia-reperfusion injury. Functional and molecular markers of kidney injury were evaluated. To explore the molecular mechanism involved the expression levels of renal HIF-1 and associated proteins were evaluated.
*Results: The blood urea nitrogen and serum creatinine levels and the histologic renal injury scores were significantly lower in 32C ischemia-reperfusion than 37C ischemia-reperfusion kidneys (all P values < .05). The expression levels of Bax and caspase-3 and the extent of TUNEL and 8-OHdG cell positivity decreased, whereas the renal Bcl-2 level increased, in 32C ischemia-reperfusion compared to 37C ischemia-reperfusion mice. The extent of renal ERK phosphorylation was significantly higher in ischemia-reperfusion than sham-operated kidneys. Also, ERK phosphorylation was significantly increased in the kidneys of 32C compared to 37C ischemia-reperfusion mice. PD98059 treatment of 32C ischemia-reperfusion mice significantly decreased the renal HIF-1 level (P < .05) and increased the BUN, s-Cr, renal Bax, and caspase-3 expression levels; the tissue injury score; and the proportions of TUNEL- and 8-OHdG-positive cells. PD98059 also increased the renal Bcl-2 level in such mice.
*Conclusions: Hypothermia attenuates the renal apoptosis and oxidative stress induced by ischemia-reperfusion via a mechanism involving ERK and HIF1 activation.
To cite this abstract in AMA style:Choi D, Jeong J, Lee K, Na K, Chang Y, Ham Y, Jeon J, Kim H. Hypothermic Protection Attenuates Kidney Injury in Renal Ischemia-Reperfusion Injury via Phosphorylation of ERK [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/hypothermic-protection-attenuates-kidney-injury-in-renal-ischemia-reperfusion-injury-via-phosphorylation-of-erk/. Accessed June 5, 2020.
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