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Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response()
Excessive production of unsaturated aldehydes from oxidized lipoproteins and membrane lipids is a characteristic feature of cardiovascular disease. Our previous studies show that unsaturated lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) promote autophagy in rat aortic...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757667/ https://www.ncbi.nlm.nih.gov/pubmed/24024137 http://dx.doi.org/10.1016/j.redox.2012.10.003 |
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author | Haberzettl, Petra Hill, Bradford G. |
author_facet | Haberzettl, Petra Hill, Bradford G. |
author_sort | Haberzettl, Petra |
collection | PubMed |
description | Excessive production of unsaturated aldehydes from oxidized lipoproteins and membrane lipids is a characteristic feature of cardiovascular disease. Our previous studies show that unsaturated lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) promote autophagy in rat aortic smooth muscle cells (RASMC). In this study, we examined the mechanism by which HNE induces autophagy. Exposure of RASMC to HNE led to the modification of several proteins, most of which were identified by mass spectrometry and confocal microscopy to be localized to the endoplasmic reticulum (ER). HNE stimulated the phosphorylation of PKR-like ER kinase and eukaryotic initiation factor 2α and increased heme oxygenase-1 (HO-1) abundance. HNE treatment also increased LC3-II formation and the phosphorylation of JNK and p38. Pharmacological inhibition of JNK, but not p38, prevented HNE-induced HO-1 expression and LC3-II formation. Inhibition of JNK increased cell death in HNE-treated cells. Pretreatment with the chemical chaperone phenylbutryic acid prevented LC3-II formation as well as JNK phosphorylation and HO-1 induction. Taken together, these data suggest that autophagic responses triggered by unsaturated aldehydes could be attributed, in part, to ER stress, which stimulates autophagy by a JNK-dependent mechanism and promotes cell survival during oxidative stress. |
format | Online Article Text |
id | pubmed-3757667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-37576672013-09-10 Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response() Haberzettl, Petra Hill, Bradford G. Redox Biol Research Paper Excessive production of unsaturated aldehydes from oxidized lipoproteins and membrane lipids is a characteristic feature of cardiovascular disease. Our previous studies show that unsaturated lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) promote autophagy in rat aortic smooth muscle cells (RASMC). In this study, we examined the mechanism by which HNE induces autophagy. Exposure of RASMC to HNE led to the modification of several proteins, most of which were identified by mass spectrometry and confocal microscopy to be localized to the endoplasmic reticulum (ER). HNE stimulated the phosphorylation of PKR-like ER kinase and eukaryotic initiation factor 2α and increased heme oxygenase-1 (HO-1) abundance. HNE treatment also increased LC3-II formation and the phosphorylation of JNK and p38. Pharmacological inhibition of JNK, but not p38, prevented HNE-induced HO-1 expression and LC3-II formation. Inhibition of JNK increased cell death in HNE-treated cells. Pretreatment with the chemical chaperone phenylbutryic acid prevented LC3-II formation as well as JNK phosphorylation and HO-1 induction. Taken together, these data suggest that autophagic responses triggered by unsaturated aldehydes could be attributed, in part, to ER stress, which stimulates autophagy by a JNK-dependent mechanism and promotes cell survival during oxidative stress. Elsevier 2013-01-26 /pmc/articles/PMC3757667/ /pubmed/24024137 http://dx.doi.org/10.1016/j.redox.2012.10.003 Text en © 2013 The Authors http://creativecommons.org/licenses/BY-license/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Haberzettl, Petra Hill, Bradford G. Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response() |
title | Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response() |
title_full | Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response() |
title_fullStr | Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response() |
title_full_unstemmed | Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response() |
title_short | Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response() |
title_sort | oxidized lipids activate autophagy in a jnk-dependent manner by stimulating the endoplasmic reticulum stress response() |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757667/ https://www.ncbi.nlm.nih.gov/pubmed/24024137 http://dx.doi.org/10.1016/j.redox.2012.10.003 |
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