Neuron-derived transthyretin modulates astrocytic glycolysis in hormone-independent manner

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Alina,Jakimowicz,Piotr,McCubrey,James A.,Rakus,Dariusz Zawiślak (Creator)
East Carolina University (ECU )
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Abstract: It has been shown that neurons alter the expression of astrocytic metabolic enzymes by secretion of until now unknown molecule(s) into extracellular fluid. Here, we present evidence that neuron-derived transthyretin (TTR) stimulates expression of glycolytic enzymes in astrocytes which is reflected by an increased synthesis of ATP. The action of TTR is restricted to regulatory enzymes of glycolysis: phosphofructokinase P (PFKP) and pyruvate kinase M1/M2 isoforms (PKM1/2). The regulation of PFK and PKM expression by TTR is presumably specific for brain tissue and is independent of the role of TTR as a carrier protein for thyroxine and retinol. TTR induced expression of PKM and PFK is mediated by the cAMP/PKA-dependent pathway and is antagonized by the PI3K/Akt pathway. Our results provide the first experimental evidence for action of TTR as a neuron-derived energy metabolism activator in astrocytes and describe the mechanisms of its action. The data presented here suggest that TTR is involved in a mechanism in which neurons stimulate degradation of glycogen-derived glucosyl units without significant modulation of glucose uptake by glial cells.

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Language: English
Date: 2017

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