Lysophosphatidic Acid Induces Aerobic Glycolysis, Lipogenesis, and Increased Amino Acid Uptake in BV-2 Microglia
| Autor: | Lisha Joshi, Ioanna Plastira, Eva Bernhart, Helga Reicher, Chintan N. Koyani, Tobias Madl, Corina Madreiter-Sokolowski, Zhanat Koshenov, Wolfgang F. Graier, Seth Hallström, Wolfgang Sattler |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Phosphocreatine
Cell Survival NF-E2-Related Factor 2 Cell Respiration Hif1α Models Biological fatty acids Article Antioxidants Cell Line lcsh:Chemistry Mice Animals Lactic Acid Amino Acids Phosphorylation ACC lcsh:QH301-705.5 aerobic glycolysis Adenine Nucleotides Lipogenesis TOR Serine-Threonine Kinases Akt Hypoxia-Inducible Factor 1 alpha Subunit Aerobiosis Mitochondria lcsh:Biology (General) lcsh:QD1-999 mTOR lipids (amino acids peptides and proteins) Microglia Lysophospholipids Energy Metabolism Glycolysis Proto-Oncogene Proteins c-akt Metabolic Networks and Pathways |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 4 International Journal of Molecular Sciences, Vol 22, Iss 1968, p 1968 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22041968 |
| Popis: | Lysophosphatidic acid (LPA) species are a family of bioactive lipids that transmit signals via six cognate G protein-coupled receptors, which are required for brain development and function of the nervous system. LPA affects the function of all cell types in the brain and can display beneficial or detrimental effects on microglia function. During earlier studies we reported that LPA treatment of microglia induces polarization towards a neurotoxic phenotype. In the present study we investigated whether these alterations are accompanied by the induction of a specific immunometabolic phenotype in LPA-treated BV-2 microglia. In response to LPA (1 µM) we observed slightly decreased mitochondrial respiration, increased lactate secretion and reduced ATP/ADP ratios indicating a switch towards aerobic glycolysis. Pathway analyses demonstrated induction of the Akt-mTOR-Hif1α axis under normoxic conditions. LPA treatment resulted in dephosphorylation of AMP-activated kinase, de-repression of acetyl-CoA-carboxylase and increased fatty acid content in the phospholipid and triacylglycerol fraction of BV-2 microglia lipid extracts, indicating de novo lipogenesis. LPA led to increased intracellular amino acid content at one or more time points. Finally, we observed LPA-dependent generation of reactive oxygen species (ROS), phosphorylation of nuclear factor erythroid 2–related factor 2 (Nrf2), upregulated protein expression of the Nrf2 target regulatory subunit of glutamate-cysteine ligase and increased glutathione synthesis. Our observations suggest that LPA, as a bioactive lipid, induces subtle alterations of the immunometabolic program in BV-2 microglia. |
| Databáze: | OpenAIRE |
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