Fructose-2,6-bisphosphate is lower in copper deficient rat cerebellum despite higher content of phosphorylated AMP-activated protein kinase.
Fructose-2,6-bisphosphate is lower in copper deficient rat cerebellum despite higher content of phosphorylated AMP-activated protein kinase.
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DOI：
10.3181/0804-rm-132
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Prohaska JR
中科院分区：
文献类型：
--
作者：
Gybina AA;Prohaska JR
铜（Cu）的限制导致发育中的大脑的病理生理学。铜缺乏损害脑线粒体，导致脑乳酸升高，提示无氧糖酵解增强。AMP激活的蛋白激酶（AMPK）是细胞能量“主开关”，其被认为通过磷酸化和激活磷酸果糖激酶2（PFK 2）增加糖酵解，导致糖酵解刺激剂果糖-2，6-二磷酸（F2，6 BP）增加。以前，铜缺乏已被证明增加小脑AMPK激活。评估了铜充足（Cu+）和铜缺乏（Cu−）大鼠幼崽的小脑，以评估Cu−小脑中AMPK激活是否具有增强PFK 2激活和增加F2，BP浓度的功能。在Cu−小脑中检测到较高水平的pAMPK。然而，PFK 2的活性，mRNA和蛋白质丰度不受铜缺乏的影响。令人惊讶的是，F2，6 BP水平在Cu−小脑中明显较低。较低的F2，6 BP可能是由于柠檬酸盐对PFK 2的抑制，因为Cu−小脑中的柠檬酸盐浓度显著较高。数据表明，Cu−小脑中AMPK的激活不会通过PFK 2机制增加糖酵解。此外，其他代谢物数据表明，糖酵解实际上可能是钝化的，因为葡萄糖和葡萄糖-6-磷酸的水平在铜小脑中高于对照组。
Limitation in copper (Cu) leads to pathophysiology in developing brain. Cu deficiency impairs brain mitochondria and results in high brain lactate suggesting augmented anaerobic glycolysis. AMP activated protein kinase (AMPK) is a cellular energy “master-switch” that is thought to augment glycolysis through phosphorylation and activation phosphofructokinase 2 (PFK2) resulting in increases of the glycolytic stimulator fructose-2,6-bisphosphate (F2,6BP). Previously, Cu deficiency has been shown to augment cerebellar AMPK activation. Cerebella of Cu-adequate (Cu+) and Cu-deficient (Cu−) rat pups were assessed to evaluate if AMPK activation in Cu− cerebella functioned to enhance PFK2 activation and increase F2,BP concentration. Higher levels of pAMPK were detected in Cu− cerebella. However, PFK2 activity, mRNA, and protein abundance were not affected by Cu deficiency. Surprisingly, F2,6BP levels were markedly lower in Cu− cerebella. Lower F2,6BP may be due to inhibition of PFK2 by citrate, as citrate concentration was significantly higher in Cu− cerebella. Data suggest AMPK activation in Cu− cerebellum does not augment glycolysis through a PFK2 mechanism. Furthermore, other metabolite data suggest that glycolysis may actually be blunted, since levels of glucose and glucose-6-phosphate were higher in Cu− cerebella than controls.