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Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy
Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have lig...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832543/ https://www.ncbi.nlm.nih.gov/pubmed/19942609 http://dx.doi.org/10.1093/carcin/bgp299 |
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author | Zabirnyk, Olga Liu, Wei Khalil, Shadi Sharma, Anit Phang, James M. |
author_facet | Zabirnyk, Olga Liu, Wei Khalil, Shadi Sharma, Anit Phang, James M. |
author_sort | Zabirnyk, Olga |
collection | PubMed |
description | Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy. |
format | Text |
id | pubmed-2832543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28325432010-03-05 Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy Zabirnyk, Olga Liu, Wei Khalil, Shadi Sharma, Anit Phang, James M. Carcinogenesis Molecular Epidemiology Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy. Oxford University Press 2010-03 2009-11-25 /pmc/articles/PMC2832543/ /pubmed/19942609 http://dx.doi.org/10.1093/carcin/bgp299 Text en © The Author 2009. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular Epidemiology Zabirnyk, Olga Liu, Wei Khalil, Shadi Sharma, Anit Phang, James M. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy |
title | Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy |
title_full | Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy |
title_fullStr | Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy |
title_full_unstemmed | Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy |
title_short | Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy |
title_sort | oxidized low-density lipoproteins upregulate proline oxidase to initiate ros-dependent autophagy |
topic | Molecular Epidemiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832543/ https://www.ncbi.nlm.nih.gov/pubmed/19942609 http://dx.doi.org/10.1093/carcin/bgp299 |
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