Revsbech Inge G, Shen Xinggui, Chakravarti Ritu, Jensen Frank B, Thiel Bonnie, Evans Alina L, Kindberg Jonas, Fröbert Ole, Stuehr Dennis J, Kevil Christopher G, Fago Angela
Department of Bioscience, Aarhus University, 8000 Aarhus C, Denmark.
Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Free Radic Biol Med. 2014 Aug;73:349-57. doi: 10.1016/j.freeradbiomed.2014.05.025. Epub 2014 Jun 5.
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.
在冬季冬眠期间，棕熊（ Ursus arctos）会在洞穴中躺上半年不吃东西，同时其基础代谢在很大程度上受到抑制。为了了解冬眠期间代谢抑制的潜在机制，我们测量了冬季冬眠和夏季活跃的斯堪的纳维亚自由放养棕熊血液中两种普遍存在的线粒体呼吸抑制剂——硫化氢（H₂S）和一氧化氮（NO）的代谢物类型和含量。我们发现，夏季活跃的熊和冬眠的熊体内硫化物代谢物的总体水平相似，但它们在血浆中的组成有显著差异，冬眠时结合型硫烷硫含量降低。高水平的未结合游离硫化物与高水平的半胱氨酸（Cys）以及低水平的结合型硫烷硫相关，这表明在冬眠期间，H₂S除了由底物Cys酶促形成外，还可能从其氧化产物（包括硫代硫酸盐和多硫化物）再生。在没有任何饮食摄入的情况下，H₂S合成模式的这种转变将有助于保留游离Cys用于合成谷胱甘肽（GSH），GSH是冬眠熊红细胞中含量很高的一种主要抗氧化剂。相比之下，作为NO代谢标志物的循环亚硝酸盐和3-磷酸甘油醛脱氢酶的红细胞S-亚硝化作用没有明显变化。我们的研究结果表明，H₂S代谢的重塑和细胞内GSH水平的提高是冬眠熊有氧代谢抑制的标志。
