Hypothermia produces rat liver proteomic changes as in hibernating mammals but decreases endoplasmic reticulum chaperones.
Hypothermia is used in the clinic for protection of organs such as the brain against ischemic injury during aortic/complex congenital cardiac surgery or post-resuscitation encephalopathy. The principal mechanism of hypothermic protection is suppression of metabolism, however, the pleiotropic effects of cooling are incompletely understood. Here, we used a rat model system to evaluate metabolic changes induced by deep hypothermia. The hypothermia-induced changes were identified using fluorescence-based two-dimensional (2-D) difference gel electrophoresis (DIGE) and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF/TOF) tandem mass spectrometry. Rats were randomly assigned to a normothermic control group (37°C, n=6) or hypothermia group (23°C, n=6) that received surface cooling for 3h. Liver tissue was excised for assessment. Functional profiling of differently expressed proteins was performed as an enrichment analysis of Gene Ontology (GO) terms and pathways. We found that the livers of anesthetized rats with deep hypothermia showed significant downregulation of proteins in the endoplasmic reticulum and mitochondria, and of those involved in ATP binding, amino acid metabolism and urea cycle, response to oxidative stress, anti-apoptosis, negative regulation of apoptosis. The changes in the proteome of the hypothermic rats showed similarities, except with regard to endoplasmic reticulum chaperones, to those identified elsewhere in mammals undergoing hibernation.
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Shimane University Faculty of Medicine, Shimane, Japan. toda@med.shimane-u.ac.jp
Teiji
T
Oda
Kouji
K
Shimizu
Akane
A
Yamaguchi
Kazumi
K
Satoh
Ken-ichi
K
Matsumoto
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D006605:Hibernation; D007035:Hypothermia / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D005227:Fatty Acids; D018832:Molecular Chaperones; D020543:Proteome; D002784:Cholesterol