Renal Mitochondrial Response to Low Temperature in Non-Hibernating and Hibernating Species.
CONCLUSIONS
Therapeutic hypothermia is commonly applied to limit ischemic injury in organ transplantation, during cardiac and brain surgery and after cardiopulmonary resuscitation. In these procedures, the kidneys are particularly at risk for ischemia/reperfusion injury (IRI), likely due to their high rate of metabolism. Although hypothermia mitigates ischemic kidney injury, it is not a panacea. Residual mitochondrial failure is believed to be a key event triggering loss of cellular homeostasis, and potentially cell death. Subsequent rewarming generates large amounts of reactive oxygen species that aggravate organ injury. Recent Advances: Hibernators are able to withstand periods of profoundly reduced metabolism and body temperature ("torpor"), interspersed by brief periods of rewarming ("arousal") without signs of organ injury. Specific adaptations allow maintenance of mitochondrial homeostasis, limit oxidative stress, and protect against cell death. These adaptations consist of active suppression of mitochondrial function and upregulation of anti-oxidant enzymes and anti-apoptotic pathways.


RESULTS
Unraveling the precise molecular mechanisms that allow hibernators to cycle through torpor and arousal without precipitating organ injury may translate into novel pharmacological approaches to limit IRI in patients.


CONCLUSIONS
Although the precise signaling routes involved in natural hibernation are not yet fully understood, torpor-like hypothermic states with increased resistance to ischemia/reperfusion can be induced pharmacologically by 5'-adenosine monophosphate (5'-AMP), adenosine, and hydrogen sulfide (H2S) in non-hibernators. In this review, we compare the molecular effects of hypothermia in non-hibernators with natural and pharmacologically induced torpor, to delineate how safe and reversible metabolic suppression may provide resistance to renal IRI. Antioxid. Redox Signal. 27, 599-617.
1 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .|2 Division of Cardiology, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
George J
GJ
Dugbartey
1 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .
Maarten C
MC
Hardenberg
1 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .
Wendelinde F
WF
Kok
3 Groningen Institute for Evolutionary Life Sciences, University of Groningen , Groningen, the Netherlands .|4 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .
Ate S
AS
Boerema
5 Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin , Madison, Wisconsin.
Hannah V
HV
Carey
6 Department of Biology, University of Western Ontario , London, Canada .
James F
JF
Staples
1 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .
Robert H
RH
Henning
1 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .|7 Department of Internal Medicine, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .
Hjalmar R
HR
Bouma
D000222:Adaptation, Physiological; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003080:Cold Temperature; D006605:Hibernation; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control; D015398:Signal Transduction
D000975:Antioxidants
free radicals; hydrogen sulfide; hypothermia; hypoxia; metabolism; mitochondria; reoxygenation