title: Hydrogen sulfide and nitric oxide metabolites in the blood of free-ranging brown bears and their potential roles in hibernation.
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.
authors.affiliation: Department of Bioscience, Aarhus University, 8000 Aarhus C, Denmark.
authors.forename: Inge G
authors.initials: IG
authors.lastname: Revsbech
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Xinggui
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Pathobiology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Chakravarti
authors.affiliation: Department of Biology, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Jensen
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Thiel
authors.affiliation: Department of Forestry and Wildlife Management, Faculty of Applied Ecology and Agricultural Sciences, Hedmark University College, Campus Evenstad, 2418 Elverum, Norway.
authors.forename: Alina L
authors.initials: AL
authors.lastname: Evans
authors.affiliation: Department of Wildlife, Fish, and Environmental Studies, Swedish University of Agricultural Sciences, 90183 Umeå, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Kindberg
authors.affiliation: Department of Cardiology, Örebro University Hospital, 70362 Örebro, Sweden.
authors.forename: Ole
authors.initials: O
authors.lastname: Fröbert
authors.affiliation: Department of Pathobiology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Stuehr
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
authors.affiliation: Department of Bioscience, Aarhus University, 8000 Aarhus C, Denmark. Electronic address: angela.fago@biology.au.dk.
authors.forename: Angela
authors.initials: A
authors.lastname: Fago
mesh_terms: D000818:Animals; D003545:Cysteine / Q000097:blood; D004734:Energy Metabolism / Q000502:physiology; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D006605:Hibernation / Q000502:physiology*; D006862:Hydrogen Sulfide / Q000097:blood* / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood*; D010101:Oxygen Consumption / Q000502:physiology; D013440:Sulfides / Q000097:blood; D001503:Ursidae / Q000378:metabolism*
chemical_list: D013440:Sulfides; D009569:Nitric Oxide; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: Adaptation; Free radicals; Hypothermia; Metabolic depression; Polysulfide; Thiosulfate