PMID- 27590616
OWN - NLM
STAT- MEDLINE
DCOM- 20170705
LR  - 20171210
IS  - 1532-7361 (Electronic)
IS  - 0039-6060 (Linking)
VI  - 161
IP  - 2
DP  - 2017 Feb
TI  - ERK phosphorylation plays an important role in the protection afforded by 
      hypothermia against renal ischemia-reperfusion injury.
PG  - 444-452
LID - S0039-6060(16)30405-6 [pii]
LID - 10.1016/j.surg.2016.07.028 [doi]
AB  - BACKGROUND: 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. METHODS: C57Bl/6 mice were divided 
      into the following groups: sham-operated (cold, 32 degrees C) vs normal temperature 
      (37 degrees C); ischemia-reperfusion mice (32 degrees C vs 37 degrees C); and PD98059- or vehicle-treated 
      ischemia-reperfusion mice (32 degrees 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. RESULTS: The blood urea nitrogen (BUN) and serum 
      creatinine (s-Cr) levels and the histologic renal injury scores were 
      significantly lower in 32 degrees C ischemia-reperfusion than 37 degrees 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 degrees C ischemia-reperfusion compared to 37 degrees 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 degrees C compared 
      to 37 degrees C ischemia-reperfusion mice. PD98059 treatment of 32 degrees 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. CONCLUSION: Hypothermia attenuates the renal 
      apoptosis and oxidative stress induced by ischemia-reperfusion via a mechanism 
      involving ERK phosphorylation.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Choi, Dae Eun
AU  - Choi DE
AD  - Department of Nephrology, School of Medicine, Chungnam National University, 
      Daejeon, Korea.
FAU - Jeong, Jin Young
AU  - Jeong JY
AD  - Department of Medical Science, College of Medicine, Chungnam National University, 
      Daejeon, Korea.
FAU - Choi, Hyunsu
AU  - Choi H
AD  - Clinical Research Institute, Daejeon St. Mary Hospital, Daejeon, Korea.
FAU - Chang, Yoon Kyung
AU  - Chang YK
AD  - Department of Nephrology, College of Medicine, The Catholic University of Korea, 
      Seoul, Korea.
FAU - Ahn, Moon Sang
AU  - Ahn MS
AD  - Vascular Surgery, School of Medicine, Chungnam National University, Daejeon, 
      Korea.
FAU - Ham, Young Rok
AU  - Ham YR
AD  - Department of Nephrology, School of Medicine, Chungnam National University, 
      Daejeon, Korea.
FAU - Na, Ki Ryang
AU  - Na KR
AD  - Department of Nephrology, School of Medicine, Chungnam National University, 
      Daejeon, Korea.
FAU - Lee, Kang Wook
AU  - Lee KW
AD  - Department of Nephrology, School of Medicine, Chungnam National University, 
      Daejeon, Korea. Electronic address: kwlee@cnu.ac.kr.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160831
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biopsy, Needle
MH  - Blotting, Western
MH  - Creatinine/blood
MH  - Disease Models, Animal
MH  - Hypothermia, Induced/*methods
MH  - Immunohistochemistry
MH  - Kidney Diseases/*pathology/surgery
MH  - Kidney Function Tests
MH  - *MAP Kinase Signaling System
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphorylation
MH  - Random Allocation
MH  - Reference Values
MH  - Reperfusion Injury/*prevention & control
MH  - Role
MH  - Sensitivity and Specificity
EDAT- 2016/09/04 06:00
MHDA- 2017/07/06 06:00
CRDT- 2016/09/04 06:00
PHST- 2016/04/06 00:00 [received]
PHST- 2016/07/14 00:00 [revised]
PHST- 2016/07/29 00:00 [accepted]
PHST- 2016/09/04 06:00 [pubmed]
PHST- 2017/07/06 06:00 [medline]
PHST- 2016/09/04 06:00 [entrez]
AID - S0039-6060(16)30405-6 [pii]
AID - 10.1016/j.surg.2016.07.028 [doi]
PST - ppublish
SO  - Surgery. 2017 Feb;161(2):444-452. doi: 10.1016/j.surg.2016.07.028. Epub 2016 Aug 
      31.