Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons'' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.     

PDK4 dictates metabolic resistance to ferroptosis by suppressing pyruvate oxidation and fatty acid synthesis

1. Download : Download high-res image (112KB)
2. Download : Download full-size image

     

Orphan nuclear receptor COUP‐TFII enhances myofibroblast glycolysis leading to kidney fibrosis

Recent studies demonstrate that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP‐TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP‐TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP‐TFII in mice resulted in attenuation of injury‐induced kidney fibrosis. A non‐biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP‐TFII overexpressing fibroblasts. Overexpression of COUP‐TFII in fibroblasts also induced production of alpha‐smooth muscle actin (αSMA) and collagen 1. Knockout of COUP‐TFII decreased glycolysis and collagen 1 levels in fibroblasts. Chip‐qPCR revealed the binding of COUP‐TFII on the promoter of PGC1α. Overexpression of COUP‐TFII reduced the cellular level of PGC1α. Targeting COUP‐TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.     

抗肿瘤代谢靶标磷酸甘油酸变位酶1 及其抑制剂的研究进展

肿瘤细胞的Warburg效应是近期肿瘤代谢研究的一大热点，磷酸甘油酸变位酶1（PGAM1）在糖酵解生物通路中起着重要作用。 报道显示PGAM1在肿瘤细胞中普遍高表达，同时促进细胞增殖过程中的糖酵解和生物合成代谢通路。基于该发现，针对PGAM1进行小 分子抑制剂研究成为开发抗肿瘤药物的新思路。综述PGAM1在肿瘤细胞中的功能、意义以及PGAM1抑制剂的开发前景。     

Effects of pentachlorophenol on the bacterial denitrification process

The use of pentachlorophenol (PCP) was banned or restricted in many countries worldwide because of its adverse influences on the ecological environment and humans. However, the potential disrupting effects of PCP on denitrifying microorganisms have warranted more analysis. In this study, the impacts of PCP on denitrification were investigated by using Paracoccus denitrificans as a model denitrifying bacterium. Compared with the control, the presences of 10 and 50 μM of PCP were found to significantly decrease the denitrification efficiencies from 98.5 to 87.2% and 68.7%, respectively. The mechanism studies showed that PCP induced the generation of reactive oxygen species, which decreased the vital enzymes activities related to glycolysis process, causing the disturbance of the metabolism of P. denitrificans utilizing carbon source (glucose) and the growth of the cell, and subsequently the generation of electron donor (NADH) for denitrification via NAD⁺ reduction was severely depressed. Further studies indicated that PCP also decreased the genes expression of several key enzymes responsible for denitrification, such as napA of nitrate reductase (NAR), nirS of nitrite reductase, norB of nitric oxide reductase, and nosZ of nitrous oxide reductase; however, there was only the enzyme activity of NAR was remarkably inhibited.     

The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages

1. Download : Download high-res image (209KB)
2. Download : Download full-size image

     

Neurons require glucose uptake and glycolysis in vivo

1. Download : Download high-res image (246KB)
2. Download : Download full-size image

     

Endogenous PP2A inhibitor CIP2A degradation by chaperone-mediated autophagy contributes to the antitumor effect of mitochondrial complex I inhibition

1. Download : Download high-res image (188KB)
2. Download : Download full-size image