Neuroglobin mediates neuroprotection of hypoxic postconditioning against transient global cerebral ischemia in rats through preserving the activity of Na(+)/K(+) ATPases.
Neuroglobin mediates neuroprotection of hypoxic postconditioning against transient global cerebral ischemia in rats through preserving the activity of Na(+)/K(+) ATPases.
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神经球蛋白通过保护 Na( )/K( ) ATP 酶的活性介导大鼠短暂性全脑缺血缺氧后处理的神经保护作用。
DOI：
10.1038/s41419-018-0656-0
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发表时间：
2018-05-25
影响因子：
9
通讯作者：
Xu E
中科院分区：
文献类型：
--
作者：
Wen H;Liu L;Zhan L;Liang D;Li L;Liu D;Sun W;Xu E
低氧后处理(HPC)是一种新的神经保护策略，对成年大鼠海马神经元具有抗短暂性全脑缺血(TGCI)的细胞保护作用。然而，其分子机制尚未完全阐明。脑红蛋白(NGB)是一种具有低氧诱导特性的内源性神经保护剂，其在实验性卒中中的作用日益受到重视。因此，本研究旨在探讨NGB在HPC介导的神经保护中的作用，并进一步探讨其潜在的分子机制。我们发现HPC在tGCI后增加了CA1区NGB的表达。同时，NGB反义寡核苷酸(AS-ODN)抑制NGB的表达消除了HPC介导的神经保护作用，而过度表达NGB则减轻了tGCI后CA1区神经元的损伤，表明HPC通过上调NGB而发挥神经保护作用。进一步研究表明，HPC可显著提高TGCI后大鼠脑组织Na+/K+ATPaseβ1亚单位(Atp1b1)的膜水平。此外，我们还证明了HPC后CA1中NGB的上调通过NGB-Atp1b1相互作用维持膜上Atp1b1的水平，并通过抑制活性氧(ROS)减少膜上Atp1b1的谷胱甘肽基化，最终维持NKA的活性。综上所述，这些数据表明，NGB参与了HPC对tGCI的神经保护作用，其机制是通过维持海马CA1区的NKA活性来实现的。
Hypoxic postconditioning (HPC) is an innovative neuroprotective strategy with cytoprotective effects on the hippocampal neurons against transient global cerebral ischemia (tGCI) in adult rats. However, its molecular mechanisms have not yet been adequately elucidated. Neuroglobin (Ngb) is an endogenous neuroprotectant with hypoxia-inducible property, and its role in experimental stroke has been increasingly attractive. Hence, the purpose of this study is to explore the involvement of Ngb in HPC-mediated neuroprotection and to further investigate its underlying molecular mechanism. We found that HPC increased Ngb expression in CA1 subregion after tGCI. Also, the inhibition of Ngb expression with Ngb antisense oligodeoxynucleotide (AS-ODNs) eliminated the neuroprotective effect mediated by HPC, whereas overexpression of Ngb ameliorated neuronal damage in CA1 after tGCI, indicating that HPC conferred neuroprotective effects via upregulation of Ngb. We further showed that HPC increased the membranous level of Na+/K+ ATPases β1 subunit (Atp1b1) in CA1 after tGCI. Furthermore, we demonstrated that Ngb upregulation in CA1 after HPC maintained the membranous level of Atp1b1 through Ngb–Atp1b1 interaction and reduced the glutathionylation of membranous Atp1b1 via suppression of reactive oxygen species (ROS), ultimately preserving the activity of NKA. Taken together, these data indicate that Ngb is involved in the neuroprotection of HPC against tGCI via maintenance of NKA activity in the hippocampal CA1.
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影响因子：
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