コラプシン反応媒介タンパク質2は15-deoxy -Δ12,14-prostaglandin J2標的タンパク質の一つであった

• Published in: 日本薬理学会年会要旨集 p. 3-P1-34
• Main Authors: 矢上, 達郎, 山本, 泰弘, 高馬, 宏美
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: apoptosis; prostaglandin; signal transduction
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_3-P1-34

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of factors contributed to the neurotoxicity of amyloid β, a causative protein of Alzheimer’s disease. A proteomic approach with biotinylated 15d-PGJ2 was used to identify its targets in the plasma membrane of rat cortical neurons. Previously, we have identified plasmalemmal targets as biotin-positive spots and classified into three functional proteins: glycolytic enzymes (enolase 1, enolase 2, pyruvate kinase isozymes M1/M2 and glyceraldehyde 3-phosphate dehydrogenase), molecular chaperones (heat shock protein A8 and T-complex protein 1 subunit a), cytoskeletal proteins (Actin β, F-actin-capping protein, tublin β, internexin α and glial fibrillary acidic protein). In the present study, we identified collapsin response mediator protein 2 (CRMP2) as one of membrane targets for 15d-PGJ2. This novel target is known as a cytosolic protein, suggesting its ectopic localization. 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain. Its nuclear receptor, peroxysome proliferator-activated receptor-γ, contributes to the neuroprotective effect of 15d-PGJ2, but not to the neurotoxic effect. Its membrane receptor, chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells, is not also involved in the neurotoxicity. Further studies are required to clear how 15d-PGJ2 could inhibit neurite outgrowth and induce neuronal apoptosis via CRMP2.