25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the...

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Main Authors: Jae-Seek You, HyangI Lim, Jeong-Yeon Seo, Kyeong-Rok Kang, Do Kyung Kim, Ji-Su Oh, Yo-Seob Seo, Gyeong-Je Lee, Jin-Soo Kim, Heung-Joong Kim, Sun-Kyoung Yu, Jae-Sung Kim
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/1/199
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author Jae-Seek You
HyangI Lim
Jeong-Yeon Seo
Kyeong-Rok Kang
Do Kyung Kim
Ji-Su Oh
Yo-Seob Seo
Gyeong-Je Lee
Jin-Soo Kim
Heung-Joong Kim
Sun-Kyoung Yu
Jae-Sung Kim
author_facet Jae-Seek You
HyangI Lim
Jeong-Yeon Seo
Kyeong-Rok Kang
Do Kyung Kim
Ji-Su Oh
Yo-Seob Seo
Gyeong-Je Lee
Jin-Soo Kim
Heung-Joong Kim
Sun-Kyoung Yu
Jae-Sung Kim
author_sort Jae-Seek You
collection DOAJ
description 25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.
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spelling doaj.art-441db17e7ff54fd1ae26fc9ae27603c92023-11-23T11:58:12ZengMDPI AGMolecules1420-30492021-12-0127119910.3390/molecules2701019925-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell LineJae-Seek You0HyangI Lim1Jeong-Yeon Seo2Kyeong-Rok Kang3Do Kyung Kim4Ji-Su Oh5Yo-Seob Seo6Gyeong-Je Lee7Jin-Soo Kim8Heung-Joong Kim9Sun-Kyoung Yu10Jae-Sung Kim11Departments of Oral and Maxillofacial Surgery, School of Dentistry, Chosun University, Gwangju 61452, KoreaInstitute of Dental Science, School of Dentistry, Chosun University, Gwangju 61452, KoreaInstitute of Dental Science, School of Dentistry, Chosun University, Gwangju 61452, KoreaInstitute of Dental Science, School of Dentistry, Chosun University, Gwangju 61452, KoreaInstitute of Dental Science, School of Dentistry, Chosun University, Gwangju 61452, KoreaDepartments of Oral and Maxillofacial Surgery, School of Dentistry, Chosun University, Gwangju 61452, KoreaDepartment of Oral and Maxillofacial Radiology, School of Dentistry, Chosun University, Gwangju 61452, KoreaDepartment of Prosthodontics, School of Dentistry, Chosun University, Gwangju 61452, KoreaDepartment of Oral and Maxillofacial Radiology, School of Dentistry, Chosun University, Gwangju 61452, KoreaInstitute of Dental Science, School of Dentistry, Chosun University, Gwangju 61452, KoreaInstitute of Dental Science, School of Dentistry, Chosun University, Gwangju 61452, KoreaInstitute of Dental Science, School of Dentistry, Chosun University, Gwangju 61452, Korea25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.https://www.mdpi.com/1420-3049/27/1/199oxysterol25-hydroxycholesterolapoptosisoxidative stressoxiapoptophagy
spellingShingle Jae-Seek You
HyangI Lim
Jeong-Yeon Seo
Kyeong-Rok Kang
Do Kyung Kim
Ji-Su Oh
Yo-Seob Seo
Gyeong-Je Lee
Jin-Soo Kim
Heung-Joong Kim
Sun-Kyoung Yu
Jae-Sung Kim
25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
Molecules
oxysterol
25-hydroxycholesterol
apoptosis
oxidative stress
oxiapoptophagy
title 25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
title_full 25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
title_fullStr 25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
title_full_unstemmed 25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
title_short 25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
title_sort 25 hydroxycholesterol induced oxiapoptophagy in l929 mouse fibroblast cell line
topic oxysterol
25-hydroxycholesterol
apoptosis
oxidative stress
oxiapoptophagy
url https://www.mdpi.com/1420-3049/27/1/199
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