| RRC ID |
72200
|
| Author |
Cheng A, Wang YF, Shinoda Y, Kawahata I, Yamamoto T, Jia WB, Yamamoto H, Mizobata T, Kawata Y, Fukunaga K.
|
| Title |
Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress.
|
| Journal |
Acta Pharmacol Sin
|
| Abstract |
We previously show that fatty acid-binding protein 3 (FABP3) triggers α-synuclein (Syn) accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model. But the role of fatty acid-binding protein 7 (FABP7) in the brain remains unclear. In this study we investigated whether FABP7 was involved in synucleinopathies. We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells, and treatment with arachidonic acid (100 M) significantly promoted FABP7-induced Syn aggregation, which was associated with cell death. We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with Kd value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid (ANS) assay; ligand 6 improved U251 cell survival via disrupting the FABP7-Syn interaction. We showed that activation of phospholipase A2 (PLA2) by psychosine (10 M) triggered oligomerization of endogenous Syn and FABP7, and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells (OPCs). FABP7 ligand 6 (1 M) significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death. This study demonstrates that FABP7 triggers α-synuclein oligomerization through oxidative stress, while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation, thereby rescuing glial cells and oligodendrocytes from cell death.
|
| Volume |
43(3)
|
| Pages |
552-562
|
| Published |
2022-3-1
|
| DOI |
10.1038/s41401-021-00675-8
|
| PII |
10.1038/s41401-021-00675-8
|
| PMID |
33935286
|
| PMC |
PMC8888578
|
| MeSH |
Animals
Arachidonic Acid / pharmacology
Cell Death / physiology
Fatty Acid-Binding Protein 7 / metabolism*
Humans
Male
Mice
Mice, Inbred C57BL
Neuroglia / metabolism*
Oligodendrocyte Precursor Cells / drug effects
Oligodendroglia / metabolism*
Oxidative Stress / physiology*
Phospholipases A2 / drug effects
Protein Binding / physiology
Psychosine / pharmacology
alpha-Synuclein / metabolism*
|
| IF |
5.064
|
| Resource |
| Human and Animal Cells |
KG-1-C(RCB0270) |
