Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels

Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels
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DOI:
10.1152/ajpregu.00260.2005
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发表时间:
2005-11-01
影响因子:
2.8
通讯作者:
Drew, KL
Drew, KL
中科院分区:
医学3区
文献类型:
--
作者:
Ma, YL;Zhu, XW;Drew, KL

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尽管异温性哺乳动物的缺氧耐受性已经建立,但尚不清楚这种适应性意义是否源于缺氧或其他与适温性、冬眠或觉醒相关的细胞挑战。在本研究中,血气,血红蛋白O-2饱和度(SO2),细胞和生理应激的指标进行了测定,在冬眠和常温和唤醒产热后。结果表明,动脉血氧分压(Pa-O2)和S-O2在唤醒过程中严重降低,缺氧诱导因子(HIF)-1 α在脑中积累。尽管缺氧的证据,无论是细胞或氧化应激,诱导型一氧化氮合酶(iNOS)的水平和生物分子的氧化修饰,观察到从冬眠后期觉醒。与大鼠相比,冬眠的北极地松鼠(Spermophilus parryii)的氧合良好,没有证据表明细胞应激,炎症反应,神经元病理学或氧化修饰后的唤醒所需的高代谢需求的时期。相比之下,适温的北极地松鼠经历轻微的慢性缺氧,低S-O2和HIF-1 α和iNOS的积累,并在大脑中表现出最大程度的细胞应激。这些结果表明,北极地松鼠的经验和耐受内源性缺氧在常温和唤醒。
Although hypoxia tolerance in heterothermic mammals is well established, it is unclear whether the adaptive significance stems from hypoxia or other cellular challenge associated with euthermy, hibernation, or arousal. In the present study, blood gases, hemoglobin O-2 saturation (SO2), and indexes of cellular and physiological stress were measured during hibernation and euthermy and after arousal thermogenesis. Results show that arterial O-2 tension (Pa-O2) and S-O2 are severely diminished during arousal and that hypoxia-inducible factor (HIF)-1 alpha accumulates in brain. Despite evidence of hypoxia, neither cellular nor oxidative stress, as indicated by inducible nitric oxide synthase (iNOS) levels and oxidative modification of biomolecules, was observed during late arousal from hibernation. Compared with rats, hibernating Arctic ground squirrels (Spermophilus parryii) are well oxygenated with no evidence of cellular stress, inflammatory response, neuronal pathology, or oxidative modification following the period of high metabolic demand necessary for arousal. In contrast, euthermic Arctic ground squirrels experience mild, chronic hypoxia with low S-O2 and accumulation of HIF-1 alpha and iNOS and demonstrate the greatest degree of cellular stress in brain. These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal.