GPR183 Regulates 7α,25-Dihydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell

Autor: Jae-Sung Kim, HyangI Lim, Jeong-Yeon Seo, Kyeong-Rok Kang, Sun-Kyoung Yu, Chun Sung Kim, Do Kyung Kim, Heung-Joong Kim, Yo-Seob Seo, Gyeong-Je Lee, Jae-Seek You, Ji-Su Oh
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecules, Vol 27, Iss 15, p 4798 (2022)
Druh dokumentu: article
ISSN: 1420-3049
45888132
DOI: 10.3390/molecules27154798
Popis: 7α,25-dihydroxycholesterol (7α,25-DHC) is an oxysterol synthesized from 25-hydroxycholesterol by cytochrome P450 family 7 subfamily B member 1 (CYP7B1) and is a monooxygenase (oxysterol-7α-hydroxylase) expressed under inflammatory conditions in various cell types. In this study, we verified that 7α,25-DHC-induced oxiapoptophagy is mediated by apoptosis, oxidative stress, and autophagy in L929 mouse fibroblasts. MTT assays and live/dead cell staining revealed that cytotoxicity was increased by 7α,25-DHC in L929 cells. Consequentially, cells with condensed chromatin and altered morphology were enhanced in L929 cells incubated with 7α,25-DHC for 48 h. Furthermore, apoptotic population was increased by 7α,25-DHC exposure through the cascade activation of caspase-9, caspase-3, and poly (ADP-ribose) polymerase in the intrinsic pathway of apoptosis in these cells. 7α,25-DHC upregulated reactive oxygen species (ROS) in L929 cells. Expression of autophagy biomarkers, including beclin-1 and LC3, was significantly increased by 7α,25-DHC treatment in L929 cells. 7α,25-DHC inhibits the phosphorylation of Akt associated with autophagy and increases p53 expression in L929 cells. In addition, inhibition of G-protein-coupled receptor 183 (GPR183), a receptor of 7α,25-DHC, using GPR183 specific antagonist NIBR189 suppressed 7α,25-DHC-induced apoptosis, ROS production, and autophagy in L929 cells. Collectively, GPR183 regulates 7α,25-DHC-induced oxiapoptophagy in L929 cells.
Databáze: Directory of Open Access Journals
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