Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase.
Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase.
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DOI：
10.1007/s12035-018-1174-x
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发表时间：
2019-03
影响因子：
5.1
通讯作者：
Oliver PL
中科院分区：
文献类型：
--
作者：
Finelli MJ;Paramo T;Pires E;Ryan BJ;Wade-Martins R;Biggin PC;McCullagh J;Oliver PL
葡萄糖代谢对大脑至关重要：它不仅为细胞功能和通信提供所需的能量，而且还参与平衡神经元中的氧化应激水平。在神经退行性疾病中已经描述了葡萄糖代谢的缺陷;然而，仍然不清楚这一基本过程如何导致这些疾病中的神经元细胞死亡。在这里，我们研究了在缺乏抗氧化性1（Oxr 1）的共济失调小鼠模型中驱动选择性神经变性的分子机制，并发现了这种蛋白质作为糖酵解酶葡萄糖-6-磷酸异构酶（GPI/Gpi 1）的调节剂的意想不到的功能。最初，我们提出了一个失调的葡萄糖代谢的代谢产物在症状前阶段的Oxr 1基因敲除小脑。然后，我们证明Oxr 1和Gpi 1在物理和功能上相互作用，并且当Oxr 1在体内缺失时，Gpi 1寡聚化水平会被破坏。此外，我们表明，Oxr 1调节Gpi 1作为细胞因子和神经保护因子的其他和不太了解的作用。总的来说，我们的数据确定了Oxr 1的新分子功能，确立了这种蛋白质作为神经元存活的重要参与者，调节大脑中的氧化应激和葡萄糖代谢。本文的在线版本（10.1007/s12035-018-1174-x）包含补充材料，可供授权用户使用。
Glucose metabolism is essential for the brain: it not only provides the required energy for cellular function and communication but also participates in balancing the levels of oxidative stress in neurons. Defects in glucose metabolism have been described in neurodegenerative disease; however, it remains unclear how this fundamental process contributes to neuronal cell death in these disorders. Here, we investigated the molecular mechanisms driving the selective neurodegeneration in an ataxic mouse model lacking oxidation resistance 1 (Oxr1) and discovered an unexpected function for this protein as a regulator of the glycolytic enzyme, glucose-6-phosphate isomerase (GPI/Gpi1). Initially, we present a dysregulation of metabolites of glucose metabolism at the pre-symptomatic stage in the Oxr1 knockout cerebellum. We then demonstrate that Oxr1 and Gpi1 physically and functionally interact and that the level of Gpi1 oligomerisation is disrupted when Oxr1 is deleted in vivo. Furthermore, we show that Oxr1 modulates the additional and less well-understood roles of Gpi1 as a cytokine and neuroprotective factor. Overall, our data identify a new molecular function for Oxr1, establishing this protein as important player in neuronal survival, regulating both oxidative stress and glucose metabolism in the brain. The online version of this article (10.1007/s12035-018-1174-x) contains supplementary material, which is available to authorized users.
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影响因子：
2.3
作者：
Fujii, H;Kanno, H;Miwa, S
通讯作者：
Miwa, S
影响因子：
3.7
作者：
Bayo J;Fiore E;Aquino JB;Malvicini M;Rizzo M;Peixoto E;Andriani O;Alaniz L;Piccioni F;Bolontrade M;Podhajcer O;Garcia MG;Mazzolini G
通讯作者：
Mazzolini G
影响因子：
14.8
作者：
Brewer, Gregory J.;Torricelli, John R.
通讯作者：
Torricelli, John R.
DOI：
10.1007/bf00320579
发表时间：
1986-07-01
期刊：
BLUT
影响因子：
--
作者：
EBER, SW;GAHR, M;SCHROTER, W
通讯作者：
SCHROTER, W
影响因子：
4.7
作者：
Emir UE;Brent Clark H;Vollmers ML;Eberly LE;Öz G
通讯作者：
Öz G