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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2021-12-01
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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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