Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro.

Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro.
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大鼠新皮质细胞在体内和分离的神经末端在体外对果糖的摄取和代谢。

DOI:
10.1111/jnc.13079
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发表时间:
2015-05
影响因子:
4.7
通讯作者:
Rise F
Rise F
中科院分区:
医学2区
文献类型:
--
作者:
Hassel B;Elsais A;Frøland AS;Taubøll E;Gjerstad L;Quan Y;Dingledine R;Rise F

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果糖与大脑中的蛋白质自发反应,形成晚期糖基化终产物(AGE),可能引起神经炎症并导致大脑病理学,包括阿尔茨海默病。我们研究了果糖是否被新皮层的氧化代谢所消除。将[14 C]果糖或其AGE倾向代谢物[14 C]甘油醛注射到大鼠体内新皮层中导致14 C标记的丙氨酸、谷氨酸、天冬氨酸、GABA和谷氨酰胺的形成。在分离的新皮质神经末梢中,[14 C]果糖标记谷氨酸、GABA和天冬氨酸,表明果糖被神经末梢摄取,这些结构中的果糖氧化代谢。己糖激酶1,通道果糖糖酵解,是高度表达的,和酶的活性是类似的果糖或葡萄糖作为底物,而果糖特异性酮己糖激酶弱表达。果糖转运蛋白Glut5的表达水平仅为神经元葡萄糖转运蛋白Glut3的约4%,表明脑细胞质膜转运是细胞外果糖清除的限制因素。果糖可以通过多元醇途径由葡萄糖形成。编码这一途径的酶,醛糖还原酶和山梨醇脱氢酶的基因在大鼠新皮层中表达。我们的结论是,果糖被运送到新皮质细胞,包括神经末梢,它是代谢,从而主要通过己糖激酶活性解毒。
Fructose reacts spontaneously with proteins in the brain to form advanced glycation end products (AGE) that may elicit neuroinflammation and cause brain pathology, including Alzheimer’s disease. We investigated whether fructose is eliminated by oxidative metabolism in neocortex. Injection of [14C]fructose or its AGE-prone metabolite [14C]glyceraldehyde into rat neocortex in vivo led to formation of 14C-labeled alanine, glutamate, aspartate, GABA, and glutamine. In isolated neocortical nerve terminals, [14C]fructose labeled glutamate, GABA, and aspartate, indicating uptake of fructose into nerve terminals and oxidative fructose metabolism in these structures. Hexokinase 1, which channels fructose into glycolysis, was highly expressed, and enzyme activity was similar with fructose or glucose as substrates, whereas the fructose-specific ketohexokinase was weakly expressed. The fructose transporter Glut5 was expressed at only ~4% of the level of neuronal glucose transporter Glut3, suggesting transport across plasma membranes of brain cells as the limiting factor in removal of extracellular fructose. Fructose may be formed from glucose through the polyol pathway. The genes encoding enzymes of this pathway, aldose reductase and sorbitol dehydrogenase, were expressed in rat neocortex. We conclude that fructose is transported into neocortical cells, including nerve terminals, and that it is metabolized and thereby detoxified primarily through hexokinase activity.
DOI: 10.1111/j.1528-1167.2010.02545.x
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