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- Revsbech, Inge G., et al.
(författare)
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Hydrogen sulfide and nitric oxide metabolites in the blood of free-ranging brown bears and their potential roles in hibernation
- 2014
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Ingår i: Free Radical Biology & Medicine. - : Elsevier. - 0891-5849 .- 1873-4596. ; 73, s. 349-357
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Tidskriftsartikel (refereegranskat)abstract
- During winter hibernation, brown bears (Ursus arctos) lie in dens for half a year without eating while their basal metabolism is largely suppressed. To understand the underlying mechanisms of metabolic depression in hibernation, we measured type and content of blood metabolites of two ubiquitous inhibitors of mitochondrial respiration, hydrogen sulfide (H2S) and nitric oxide (NO), in winter-hibernating and summer-active free-ranging Scandinavian brown bears. We found that levels of sulfide metabolites were overall similar in summer-active and hibernating bears but their composition in the plasma differed significantly, with a decrease in bound sulfane sulfur in hibernation. High levels of unbound free sulfide correlated with high levels of cysteine (Cys) and with low levels of bound sulfane sulfur, indicating that during hibernation H2S, in addition to being formed enzymatically from the substrate Cys, may also be regenerated from its oxidation products, including thiosulfate and polysulfides. In the absence of any dietary intake, this shift in the mode of H2S synthesis would help preserve free Cys for synthesis of glutathione (GSH), a major antioxidant found at high levels in the red blood cells of hibernating bears. In contrast, circulating nitrite and erythrocytic S-nitrosation of glyceraldehyde-3-phosphate dehydrogenase, taken as markers of NO metabolism, did not change appreciably. Our findings reveal that remodeling of H2S metabolism and enhanced intracellular GSH levels are hallmarks of the aerobic metabolic suppression of hibernating bears.
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| 2. |
- Revsbech, Inge G., et al.
(författare)
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Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bear Ursus arctos
- 2013
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 304:1, s. R43-R49
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Tidskriftsartikel (refereegranskat)abstract
- Revsbech IG, Malte H, Frobert O, Evans A, Blanc S, Josefsson J, Fago A. Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bear Ursus arctos. Am J Physiol Regul Integr Comp Physiol 304: R43-R49, 2013. First published November 21, 2012; doi:10.1152/ajpregu.00440.2012.-During winter hibernation, brown bears (Ursus arctos) reduce basal O-2 consumption rate to similar to 25% compared with the active state, while body temperature decreases moderately (to similar to 30 degrees C), suggesting a temperature-independent component in their metabolic depression. To establish whether changes in O-2 consumption during hibernation correlate with changes in blood O-2 affinity, we took blood samples from the same six individuals of hibernating and nonhibernating free-ranging brown bears during winter and summer, respectively. A single hemoglobin (Hb) component was detected in all samples, indicating no switch in Hb synthesis. O-2 binding curves measured on red blood cell lysates at 30 degrees C and 37 degrees C showed a less temperature-sensitive O-2 affinity than in other vertebrates. Furthermore, hemolysates from hibernating bears consistently showed lower cooperativity and higher O-2 affinity than their summer counterparts, regardless of the temperature. We found that this increase in O-2 affinity was associated with a significant decrease in the red cell Hb-cofactor 2,3-diphosphoglycerate (DPG) during hibernation to approximately half of the summer value. Experiments performed on purified Hb, to which DPG had been added to match summer and winter levels, confirmed that the low DPG content was the cause of the left shift in the Hb-O-2 equilibrium curve during hibernation. Levels of plasma lactate indicated that glycolysis is not upregulated during hibernation and that metabolism is essentially aerobic. Calculations show that the increase in Hb-O-2 affinity and decrease in cooperativity resulting from decreased red cell DPG may be crucial in maintaining a fairly constant tissue oxygen tension during hibernation in vivo.
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| 3. |
- Welinder, Karen Gjesing, et al.
(författare)
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Biochemical Foundations of Health and Energy Conservation in Hibernating Free-Ranging Subadult Brown Bear Ursus arctos
- 2016
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Ingår i: Journal of Biological Chemistry. - Rockville, USA : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 291:43, s. 22509-22523
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Tidskriftsartikel (refereegranskat)abstract
- Brown bears (Ursus arctos) hibernate for 5-7 months without eating, drinking, urinating and defecating at a metabolic rate of only 25% of the summer activity rate. Nonetheless, they emerge healthy and alert in spring. We quantified the biochemical adaptations for hibernation by comparing the proteome, metabolome, and hematologic features of blood from hibernating and active free-ranging subadult brown bears with a focus on conservation of health and energy. We found that total plasma protein concentration increased during hibernation, even though the concentrations of most individual plasma proteins decreased, as did the white blood cell types. Strikingly, antimicrobial defense proteins increased in concentration. Central functions in hibernation involving the coagulation response and protease inhibition, as well as lipid transport and metabolism, were upheld by increased levels of very few key or broad-specificity proteins. The changes in coagulation factor levels matched the changes in activity measurements. A dramatic 45-fold increase in sex-hormone-binding-globulin SHBG levels during hibernation draws, for the first time, attention to its significant but unknown role in maintaining hibernation physiology. We propose that energy for the costly protein synthesis is reduced by three mechanisms, (i) dehydration, which increases protein concentration without de novo synthesis; (ii) reduced protein degradation rates due to a 6 °C reduction in body temperature, and decreased protease activity; and (iii) a marked redistribution of energy resources only increasing de novo synthesis of few key proteins. This comprehensive global data identified novel biochemical strategies for bear adaptations to the extreme condition of hibernation, and have implications for our understanding of physiology in general.
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