Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, 2100, Copenhagen, Denmark.
Neurochem Res. 2017 Sep;42(9):2490-2494. doi: 10.1007/s11064-017-2267-z. Epub 2017 May 11.
Glycogen is the main storage form of glucose in the brain. In contrast with previous beliefs, brain glycogen has recently been shown to play important roles in several brain functions. A fraction of metabolized glucose molecules are being shunted through glycogen before reentering the glycolytic pathway, a phenomenon known as the glycogen shunt. The significance of glycogen in astrocyte energetics is underlined by high activity of the glycogen shunt and the finding that inhibition of glycogen degradation, under some conditions leads to a disproportional increase in glycolytic activity, so-called glycolytic supercompensation. Glycogen phosphorylase, the key enzyme in glycogen degradation, is expressed in two different isoforms in brain, the muscle and the brain isoform. Recent studies have illustrated how these are differently regulated. In the present study, we investigate the role of the two isoforms in glycolytic supercompensation in cultured astrocytes with the expression of either one of the isoforms silenced by siRNA knockdown. When reintroducing glucose to glucose-starved astrocytes, glycolytic activity increased dramatically. Interestingly, the increase was 30% higher in astrocytes not expressing the muscle isoform of glycogen phosphorylase. Based on these results and previously published data we couple the muscle isoform of glycogen phosphorylase to glycolytic supercompensation and glycogen shunt activity, giving insights to the underlying mechanistic of these phenomena.
糖原是大脑中葡萄糖的主要储存形式。与之前的观点相反，最近的研究表明，脑糖原在几种大脑功能中发挥着重要作用。一部分代谢的葡萄糖分子在重新进入糖酵解途径之前通过糖原分流，这种现象被称为糖原分流。糖原在星形胶质细胞能量学中的重要性突出表现在糖原分流的高活性以及发现，在某些条件下，抑制糖原降解会导致糖酵解活性不成比例地增加，即所谓的糖酵解超代偿。糖原磷酸化酶是糖原降解的关键酶，在大脑中表达两种不同的同工酶，即肌肉同工酶和脑同工酶。最近的研究说明了这两种同工酶是如何不同地被调节的。在本研究中，我们通过 siRNA 敲低沉默一种同工酶的表达，研究了这两种同工酶在培养的星形胶质细胞中糖酵解超代偿中的作用。当向葡萄糖饥饿的星形胶质细胞中重新引入葡萄糖时，糖酵解活性显著增加。有趣的是，在不表达肌肉型糖原磷酸化酶同工酶的星形胶质细胞中，增加了 30%。基于这些结果和以前发表的数据，我们将肌肉型糖原磷酸化酶同工酶与糖酵解超代偿和糖原分流活性联系起来，深入了解这些现象的潜在机制。
