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Biochemical Foundations of Health and Energy Conservation in Hibernating Free-Ranging Subadult Brown Bear Ursus arctos
Department of Chemistry and Bioscience, Section of Biotechnology, Aalborg University, Aalborg, Denmark.
Department of Chemistry and Bioscience, Section of Biotechnology, Aalborg University, Aalborg, Denmark; Wellspring Biosciences LLC, San Diego CA, United States.
Department of Chemistry and Bioscience, Section of Biotechnology, Aalborg University, Aalborg, Denmark.
Department of Chemistry and Bioscience, Section of Biotechnology, Aalborg University, Aalborg, Denmark.
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2016 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 43, p. 22509-22523Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Rockville, USA: American Society for Biochemistry and Molecular Biology, 2016. Vol. 291, no 43, p. 22509-22523
Keywords [en]
Antimicrobial proteins, blood constituents, coagulation factor, complement system, hibernation physiology, metabolomics, protein turnover, proteomics, sex hormone-binding globulin (SHBG)
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:oru:diva-52176DOI: 10.1074/jbc.M116.742916ISI: 000386760600013PubMedID: 27609515Scopus ID: 2-s2.0-84992343533OAI: oai:DiVA.org:oru-52176DiVA, id: diva2:972609
Note

Funding Agency:

Lundbech Foundation R126-2012-12408

Aalborg University

Available from: 2016-09-21 Created: 2016-09-14 Last updated: 2018-07-16Bibliographically approved
In thesis
1. Immobilization as a risk factor for arterial and venous thrombosis
Open this publication in new window or tab >>Immobilization as a risk factor for arterial and venous thrombosis
2018 (Swedish)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Aim: Immobilization and a sedentary lifestyle are correlated with an elevated risk of both arterial and venous thrombosis. The goal of this research was to investigate whether markers associated with cardiovascular disease risk are altered during long term immobilization in a human model and in the brown bear, which survives annual cycles of long-term immobilization.

Methods: In study populations assigned to 20-60 days of strict head-down-tilt bed rest 24h a day, we analysed blood levels of the emerging cardiovascular disease marker cystatin C, soluble markers of in vivo platelet activation P-selectin and PDGF-BB, and platelet aggregation. Blood samples were taken from free-ranging brown bears in summer and again during hibernation for analysis of lipid profile and platelet aggregation. Histological examination was performed on the left anterior descending coronary artery and aortic arches of bears harvested during the hunting season.

Results: During prolonged bed rest in humans, levels of cystatin C and platelet aggregation remained unchanged, but we observed a significant decrease in platelet activation markers. Brown bear plasma lipids were elevated during hibernation compared with the active state and cholesterol levels were generally considerably higher than normal human values. The arterial specimens showed no signs of atherosclerosis. Platelet aggregation was halved during hibernation compared to the active state.

Conclusions: Long-term immobilization has effects on several cardiovascular risk factors in both humans and bears. Increased knowledge and understanding of the protective mechanisms that allows the brown bear to survive repeated periods of immobilization could contribute to new strategies for prevention and treatment of cardiovascular disease in humans.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2018. p. 69
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 179
Keywords
Venous thrombosis, arterial thrombosis, atherosclerosis, cystatin C, cholesterol, platelet activation, platelet aggregation, immobilization
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-65003 (URN)978-91-7529-243-4 (ISBN)
Public defence
2018-06-07, Örebro universitet, Campus USÖ, hörsal C3, Södra Grev Rosengatan 32, Örebro, 09:15 (Swedish)
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Supervisors
Available from: 2018-02-14 Created: 2018-02-14 Last updated: 2018-05-15Bibliographically approved

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Arinell, Karin

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