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GPR183 Regulates 7α,25-Dihydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell
by
Lee, Gyeong-Je
, Lim, HyangI
, Seo, Yo-Seob
, Kim, Jae-Sung
, Seo, Jeong-Yeon
, Kim, Chun Sung
, Kang, Kyeong-Rok
, Yu, Sun-Kyoung
, Kim, Do Kyung
, Oh, Ji-Su
, Kim, Heung-Joong
, You, Jae-Seek
in
7α,25-dihydroxycholesterol
/ Animals
/ apoptosis
/ Apoptosis - genetics
/ Apoptosis - physiology
/ Autophagy - genetics
/ Autophagy - physiology
/ cholesterol
/ Fibroblasts - metabolism
/ Hydroxycholesterols - metabolism
/ Mice
/ oxiapoptophagy
/ oxidative stress
/ oxysterol
/ Oxysterols - metabolism
/ Reactive Oxygen Species - metabolism
/ Receptors, G-Protein-Coupled - metabolism
2022
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GPR183 Regulates 7α,25-Dihydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell
by
Lee, Gyeong-Je
, Lim, HyangI
, Seo, Yo-Seob
, Kim, Jae-Sung
, Seo, Jeong-Yeon
, Kim, Chun Sung
, Kang, Kyeong-Rok
, Yu, Sun-Kyoung
, Kim, Do Kyung
, Oh, Ji-Su
, Kim, Heung-Joong
, You, Jae-Seek
in
7α,25-dihydroxycholesterol
/ Animals
/ apoptosis
/ Apoptosis - genetics
/ Apoptosis - physiology
/ Autophagy - genetics
/ Autophagy - physiology
/ cholesterol
/ Fibroblasts - metabolism
/ Hydroxycholesterols - metabolism
/ Mice
/ oxiapoptophagy
/ oxidative stress
/ oxysterol
/ Oxysterols - metabolism
/ Reactive Oxygen Species - metabolism
/ Receptors, G-Protein-Coupled - metabolism
2022
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GPR183 Regulates 7α,25-Dihydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell
by
Lee, Gyeong-Je
, Lim, HyangI
, Seo, Yo-Seob
, Kim, Jae-Sung
, Seo, Jeong-Yeon
, Kim, Chun Sung
, Kang, Kyeong-Rok
, Yu, Sun-Kyoung
, Kim, Do Kyung
, Oh, Ji-Su
, Kim, Heung-Joong
, You, Jae-Seek
in
7α,25-dihydroxycholesterol
/ Animals
/ apoptosis
/ Apoptosis - genetics
/ Apoptosis - physiology
/ Autophagy - genetics
/ Autophagy - physiology
/ cholesterol
/ Fibroblasts - metabolism
/ Hydroxycholesterols - metabolism
/ Mice
/ oxiapoptophagy
/ oxidative stress
/ oxysterol
/ Oxysterols - metabolism
/ Reactive Oxygen Species - metabolism
/ Receptors, G-Protein-Coupled - metabolism
2022
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GPR183 Regulates 7α,25-Dihydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell
Journal Article
GPR183 Regulates 7α,25-Dihydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell
2022
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Overview
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.
Publisher
MDPI,MDPI AG
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