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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...

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Autores principales: Zabirnyk, Olga, Liu, Wei, Khalil, Shadi, Sharma, Anit, Phang, James M.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
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.
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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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AT sharmaanit oxidizedlowdensitylipoproteinsupregulateprolineoxidasetoinitiaterosdependentautophagy
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