1-O-alkyl glycerophosphate-induced CD36 expression drives oxidative stress in microglial cells

•AGP induces PPARγ activation in primary microglial cells.•AGP enhances CD36 expression through PPARγ activation.•AGP increases ROS generation and product of oxidative stress. Microglia, the tissue-resident macrophages in the central nervous system, are important for the initiation and perpetuation...

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Bibliographic Details
Published in:Cellular signalling 2020-01, Vol.65, p.109459, Article 109459
Main Author: Tsukahara, Tamotsu
Format: Article
Language:English
Subjects:
Animals
CCL7
CD36
CD36 Antigens - genetics
CD36 Antigens - metabolism
Cell Line - cytology
Cells, Cultured
Chemokine CCL7 - genetics
Chemokine CCL7 - metabolism
Gene Expression Regulation - drug effects
Glycerophosphates - pharmacology
Inflammation - metabolism
Lipid Peroxidation - genetics
Lysophospholipids
Mice
Mice, Inbred C57BL
Microglia
Microglia - cytology
Microglia - drug effects
Microglia - metabolism
Oxidative stress
Oxidative Stress - drug effects
PPAR gamma - antagonists & inhibitors
PPAR gamma - metabolism
Reactive oxygen species
Reactive Oxygen Species - metabolism
RNA, Small Interfering
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Summary:•AGP induces PPARγ activation in primary microglial cells.•AGP enhances CD36 expression through PPARγ activation.•AGP increases ROS generation and product of oxidative stress. Microglia, the tissue-resident macrophages in the central nervous system, are important for the initiation and perpetuation of neuroinflammation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-inducible transcription factor and plays an important role in fatty acid metabolism. Our previous study found that 1-O-alkyl glycerophosphate (AGP), a naturally occurring ether analog of lysophosphatidic acid, is a high-affinity, partial agonist of PPARγ. In this study, we investigated the role of AGP in microglial activation and illustrated the underlying molecular mechanism. We found that AGP treatment increased the production of intracellular reactive oxygen species and induced PPARγ activation in microglial cells. Interestingly, AGP also up-regulated the expression levels of the cluster of differentiation 36 (CD36) scavenger receptor, a high-affinity receptor for oxidized low-density lipoproteins. The findings suggest that AGP induces PPARγ activation, enhances CD36 expression and increases the production of intracellular reactive oxygen species (ROS) in microglial cells.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2019.109459