FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes
Open Access
- 19 August 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Neurobiology
- Vol. 57 (12), 4891-4910
- https://doi.org/10.1007/s12035-020-02057-3
Abstract
Fatty acid binding protein 7 (FABP7) is an intracellular fatty acid chaperon that is highly expressed in astrocytes, oligodendrocyte-precursor cells, and malignant glioma. Previously, we reported that FABP7 regulates the response to extracellular stimuli by controlling the expression of caveolin-1, an important component of lipid raft. Here, we explored the detailed mechanisms underlying FABP7 regulation of caveolin-1 expression using primary cultured FABP7-KO astrocytes as a model of loss of function and NIH-3T3 cells as a model of gain of function. We discovered that FABP7 interacts with ATP-citrate lyase (ACLY) and is important for acetyl-CoA metabolism in the nucleus. This interaction leads to epigenetic regulation of several genes, including caveolin-1. Our novel findings suggest that FABP7-ACLY modulation of nuclear acetyl-CoA has more influence on histone acetylation than cytoplasmic acetyl-CoA. The changes to histone structure may modify caveolae-related cell activity in astrocytes and tumors, including malignant glioma.Keywords
Funding Information
- Japan Society for the Promotion of Science (15K16206, 17K15539, 16H05116, 19H04026)
- Japan Agency for Medical Research and Development (JP17dm0107071)
- GlaxoSmithKline foundation
This publication has 55 references indexed in Scilit:
- Association of modified cytosines and the methylated DNA-binding protein MeCP2 with distinctive structural domains of lampbrush chromatinChromosome Research, 2012
- CpG island shore methylation regulates caveolin-1 expression in breast cancerOncogene, 2012
- FABP7 expression in normal and stab-injured brain cortex and its role in astrocyte proliferationHistochemistry and Cell Biology, 2011
- Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia CellsOnline Journal of Public Health Informatics, 2011
- Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen‐activated protein Kinase (MAPK) and Phosphatidylinositol‐3‐kinase (PI3K)/AKT pathwaysJournal of Cellular Physiology, 2011
- Transcriptional Repression of Caveolin-1 (CAV1) Gene Expression by GATA-6 in Bladder Smooth Muscle Hypertrophy in Mice and Human BeingsThe American Journal of Pathology, 2011
- Chronic High-Fat Diet Drives Postnatal Epigenetic Regulation of μ-Opioid Receptor in the BrainNeuropsychopharmacology, 2011
- Brain Fatty Acid-binding Protein and ω-3/ω-6 Fatty Acids: MECHANISTIC INSIGHT INTO MALIGNANT GLIOMA CELL MIGRATIONOnline Journal of Public Health Informatics, 2010
- Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndromeJournal Of Physiology-London, 2009
- Fatty acid-binding proteins: role in metabolic diseases and potential as drug targetsNature Reviews Drug Discovery, 2008