title: ERK phosphorylation plays an important role in the protection afforded by hypothermia against renal ischemia-reperfusion injury.
abstract: Although hypothermia attenuates the renal injury induced by ischemia-reperfusion, the detailed molecular pathway(s) involved remains unknown. ERK phosphorylation is known to protect against ischemia-reperfusion injury. Also, it has been reported that hypothermia may induce ERK phosphorylation in the heart and brain. We evaluated the role played by ERK in hypothermic protection against renal ischemia-reperfusion injury.
  
  
  
  C57Bl/6 mice were divided into the following groups: sham-operated (cold, 32°C) vs normal temperature (37°C); ischemia-reperfusion mice (32°C vs 37°C); and PD98059- or vehicle-treated ischemia-reperfusion mice (32°C). 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.
  
  
  
  The blood urea nitrogen (BUN) and serum creatinine (s-Cr) levels and the histologic renal injury scores were significantly lower in 32°C ischemia-reperfusion than 37°C 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 32°C ischemia-reperfusion compared to 37°C 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 32°C compared to 37°C ischemia-reperfusion mice. PD98059 treatment of 32°C 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.
  
  
  
  Hypothermia attenuates the renal apoptosis and oxidative stress induced by ischemia-reperfusion via a mechanism involving ERK phosphorylation.
authors: Department of Nephrology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors: Dae Eun
authors: DE
authors: Choi
authors: Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Korea.
authors: Jin Young
authors: JY
authors: Jeong
authors: Clinical Research Institute, Daejeon St. Mary Hospital, Daejeon, Korea.
authors: Hyunsu
authors: H
authors: Choi
authors: Department of Nephrology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Yoon Kyung
authors: YK
authors: Chang
authors: Vascular Surgery, School of Medicine, Chungnam National University, Daejeon, Korea.
authors: Moon Sang
authors: MS
authors: Ahn
authors: Department of Nephrology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors: Young Rok
authors: YR
authors: Ham
authors: Department of Nephrology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors: Ki Ryang
authors: KR
authors: Na
authors: Department of Nephrology, School of Medicine, Chungnam National University, Daejeon, Korea. Electronic address: kwlee@cnu.ac.kr.
authors: Kang Wook
authors: KW
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D001707:Biopsy, Needle; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000379:methods*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000473:pathology* / Q000601:surgery; D007677:Kidney Function Tests; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D012380:Role; D012680:Sensitivity and Specificity
chemical_list: D003404:Creatinine