Pemafibrate, a selective PPARα modulator, and fenofibrate suppress microglial activation through distinct PPARα and SIRT1-dependent pathways
| Autor: | Kento Ogawa, Hiroyuki Koyama, Daisuke Aotani, Kenro Imaeda, Hiromi Kataoka, Tomohiro Tanaka, Takashi Yagi, Hideomi Ohguchi, Katsushi Takeda, Tingting Guo |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Anti-Inflammatory Agents Biophysics Peroxisome proliferator-activated receptor Biochemistry Cell Line Mice 03 medical and health sciences 0302 clinical medicine Sirtuin 1 medicine Animals PPAR alpha Receptor Molecular Biology Inflammation chemistry.chemical_classification Benzoxazoles Gene knockdown Fenofibrate biology Microglia Cell Biology Peroxisome Cell biology Mice Inbred C57BL Butyrates 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis biology.protein Phosphorylation Signal Transduction medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 524:385-391 |
| ISSN: | 0006-291X |
| Popis: | Pemafibrate, a selective peroxisome proliferator-activated receptor (PPAR) α modulator, is a new drug that specifically modulates PPARα conformation and co-activator recruitment, thereby lowers plasma triglycerides with less off-target effects. Classical PPARα ligands such as fenofibrate suppress inflammatory cells including microglia. However, effects of pemafibrate on microglia have never been addressed. Here we show that pemafibrate, like other PPARα ligands, potently suppressed NF-κB phosphorylation and cytokine expression in microglial cells. PPARα knockdown significantly amplified LPS-induced cytokine expression. Pemafibrate-induced suppression of IL-6 expression was reversed by PPARα knockdown. However, suppression by fenofibrate was not reversed by PPARα knockdown but by Sirtuin 1 (SIRT1) knockdown. In conclusion, pemafibrate and fenofibrate similarly suppresses microglial activation but through distinct PPARα and SIRT1-dependet pathways. |
| Databáze: | OpenAIRE |
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