Astrocytes releasing glucose- and/or glycogen-derived lactate and glutamine play a crucial role in shaping neuronal function and plasticity. Little is known, however, how metabolic functions of astrocytes, e.g., their ability to degrade glucosyl units, are affected by the presence of neurons. To address this issue we carried out experiments which demonstrated that co-culturing of rat hippocampal astrocytes with neurons significantly elevates the level of mRNA and protein for crucial enzymes of glycolysis (phosphofructokinase, aldolase, and pyruvate kinase), glycogen metabolism (glycogen synthase and glycogen phosphorylase), and glutamine synthetase in astrocytes. Simultaneously, the decrease of the capability of neurons to metabolize glucose and glutamine is observed. We provide evidence that neurons alter the expression of astrocytic enzymes by secretion of as yet unknown molecule(s) into the extracellular fluid. Moreover, our data demonstrate that almost all studied enzymes may localize in astrocytic nuclei and this localization is affected by the co-culturing with neurons which also reduces proliferative activity of astrocytes. Our results provide the first experimental evidence that the astrocyte-neuron crosstalk substantially affects the expression of basal metabolic enzymes in the both types of cells and influences their subcellular localization in astrocytes.

Muscle fructose 1,6-bisphosphate aldolase (ALDA) is a glycolytic enzyme which may localize both in nuclei and cytoplasm of cells, however its role in the nuclei is unclear. Here, we demonstrate the links between subcellular localization of ALDA and the cell cycle progression as well as the availability of energetic substrates. Results of our studies indicate that nuclear localization of ALDA correlates with the proliferative activity of the cells and with the expression of Ki-67, a marker of proliferation, both in the KLN-205 (mouse lung cancer cells) and human squamous cell lung cancer cells (hSCC). Chemically-induced block of cell cycle entry in S phase and the inhibition of transcription stimulate removal of ALDA from cells nuclei suggesting that nuclear ALDA is involved in cells proliferation. On the other hand, subcellular distribution of the enzyme also depends on the stress and pro-survival signals mediated by the Akt and the p38 pathways and, in non-proliferating cells, on the availability of glucose and lactate. The results presented here point to ALDA as a factor involved in the regulation of cells proliferation.

Muscle fructose-1,6-bisphosphate aldolase (ALDOA) is among the most abundant glycolytic enzymes in all cancer cells. Here, we show that the enzyme plays a previously unknown and critical role in a cancer cell survival. Simultaneous inhibition of ALDOA activity and interaction with F-actin cytoskeleton using ALDOA slow-binding inhibitor UM0112176 leads to a rapid cofilin-dependent loss of F-actin stress fibers which is associated with elevated ROS production, inhibition of ATP synthesis, increase in calcium levels, caspase activation and arrested cellular proliferation. These effects can be reproduced by silencing of ALDOA. The mechanism of pharmacological action is, however, independent of the catalytic function of the enzyme, specific to cancer cells, and is most deleterious to cells undergoing the epithelial–mesenchymal transition, a process facilitating cancer cell invasion. Our results demonstrate that the overabundance of ALDOA in cancer cells is associated with its moonlighting rather than catalytic functions. This may have significant implications for development of novel broad-based anti-cancer therapies.

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In skeletal muscles, FBPase-aldolase complex is located on a-actinin of the Z-line. In the present paper, we show evidence that stability of the complex is regulated by calcium ions. Real time interaction analysis, confocal microscopy and the protein exchange method have revealed that elevated calcium concentration decreases association constant of FBPase-aldolase and FBPase-a-actinin complex, causes fast dissociation of FBPase from the Z-line and slow accumulation of aldolase within the I-band and M-line. Therefore, the release of Ca 2+ during muscle contraction might result, simultaneously, in the inhibition of glyconeogenesis and in the acceleration of glycolysis.