Cargando…

Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress

7-Oxysterols are major toxic components in oxidized low-density lipoprotein and human atheroma lesions, which cause lysosomal membrane permeabilization (LMP) and cell death. Autophagy may function as a survival mechanism in this process. Here, we investigated whether 7-oxysterols mixed in an atherom...

Descripción completa

Detalles Bibliográficos
Autores principales: Yuan, Xi-Ming, Sultana, Nargis, Siraj, Nabeel, Ward, Liam J., Ghafouri, Bijar, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Libertas Academica 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782829/
https://www.ncbi.nlm.nih.gov/pubmed/26966389
http://dx.doi.org/10.4137/JCD.S37841
_version_ 1782420019297124352
author Yuan, Xi-Ming
Sultana, Nargis
Siraj, Nabeel
Ward, Liam J.
Ghafouri, Bijar
Li, Wei
author_facet Yuan, Xi-Ming
Sultana, Nargis
Siraj, Nabeel
Ward, Liam J.
Ghafouri, Bijar
Li, Wei
author_sort Yuan, Xi-Ming
collection PubMed
description 7-Oxysterols are major toxic components in oxidized low-density lipoprotein and human atheroma lesions, which cause lysosomal membrane permeabilization (LMP) and cell death. Autophagy may function as a survival mechanism in this process. Here, we investigated whether 7-oxysterols mixed in an atheroma-relevant proportion induce autophagy, whether autophagy induction influences 7-oxysterol-mediated cell death, and the underlying mechanisms, by focusing on cellular lipid levels, oxidative stress, and LMP in 7-oxysterol-treated macrophages. We found that 7-oxysterols induced cellular lipid accumulation, autophagy dysfunction, and cell death in the form of both apoptosis and necrosis. Exposure to 7-oxysterols induced autophagic vacuole synthesis in the form of increased autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and LC3-phosphatidylethanolamine conjugate (LC3-II) and autophagic vacuole formation. This led to an accumulation of p62, indicating a reduction in autophagic vacuole degradation. Importantly, autophagy induction significantly reduced 7-oxysterol-mediated cell death by diminishing LMP and oxidative stress. Moreover, autophagy induction minimized cellular lipid accumulation induced by 7-oxysterols. These findings highlight the importance of autophagy in combating cellular stress, LMP, and cell death in atherosclerosis. Therefore, activation of the autophagy pathway may be a potential therapeutic strategy for prevention of necrotic core formation in atherosclerotic lesions.
format Online
Article
Text
id pubmed-4782829
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Libertas Academica
record_format MEDLINE/PubMed
spelling pubmed-47828292016-03-10 Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress Yuan, Xi-Ming Sultana, Nargis Siraj, Nabeel Ward, Liam J. Ghafouri, Bijar Li, Wei J Cell Death Original Research 7-Oxysterols are major toxic components in oxidized low-density lipoprotein and human atheroma lesions, which cause lysosomal membrane permeabilization (LMP) and cell death. Autophagy may function as a survival mechanism in this process. Here, we investigated whether 7-oxysterols mixed in an atheroma-relevant proportion induce autophagy, whether autophagy induction influences 7-oxysterol-mediated cell death, and the underlying mechanisms, by focusing on cellular lipid levels, oxidative stress, and LMP in 7-oxysterol-treated macrophages. We found that 7-oxysterols induced cellular lipid accumulation, autophagy dysfunction, and cell death in the form of both apoptosis and necrosis. Exposure to 7-oxysterols induced autophagic vacuole synthesis in the form of increased autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and LC3-phosphatidylethanolamine conjugate (LC3-II) and autophagic vacuole formation. This led to an accumulation of p62, indicating a reduction in autophagic vacuole degradation. Importantly, autophagy induction significantly reduced 7-oxysterol-mediated cell death by diminishing LMP and oxidative stress. Moreover, autophagy induction minimized cellular lipid accumulation induced by 7-oxysterols. These findings highlight the importance of autophagy in combating cellular stress, LMP, and cell death in atherosclerosis. Therefore, activation of the autophagy pathway may be a potential therapeutic strategy for prevention of necrotic core formation in atherosclerotic lesions. Libertas Academica 2016-03-07 /pmc/articles/PMC4782829/ /pubmed/26966389 http://dx.doi.org/10.4137/JCD.S37841 Text en © 2016 the author(s), publisher and licensee Libertas Academica Ltd. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.
spellingShingle Original Research
Yuan, Xi-Ming
Sultana, Nargis
Siraj, Nabeel
Ward, Liam J.
Ghafouri, Bijar
Li, Wei
Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress
title Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress
title_full Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress
title_fullStr Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress
title_full_unstemmed Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress
title_short Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress
title_sort autophagy induction protects against 7-oxysterol-induced cell death via lysosomal pathway and oxidative stress
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782829/
https://www.ncbi.nlm.nih.gov/pubmed/26966389
http://dx.doi.org/10.4137/JCD.S37841
work_keys_str_mv AT yuanximing autophagyinductionprotectsagainst7oxysterolinducedcelldeathvialysosomalpathwayandoxidativestress
AT sultananargis autophagyinductionprotectsagainst7oxysterolinducedcelldeathvialysosomalpathwayandoxidativestress
AT sirajnabeel autophagyinductionprotectsagainst7oxysterolinducedcelldeathvialysosomalpathwayandoxidativestress
AT wardliamj autophagyinductionprotectsagainst7oxysterolinducedcelldeathvialysosomalpathwayandoxidativestress
AT ghafouribijar autophagyinductionprotectsagainst7oxysterolinducedcelldeathvialysosomalpathwayandoxidativestress
AT liwei autophagyinductionprotectsagainst7oxysterolinducedcelldeathvialysosomalpathwayandoxidativestress