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Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer

An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative str...

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Autores principales: Perkovic, Matea Nikolac, Jaganjac, Morana, Milkovic, Lidija, Horvat, Tea, Rojo, David, Zarkovic, Kamelija, Ćorić, Marijana, Hudolin, Tvrtko, Waeg, Georg, Orehovec, Biserka, Zarkovic, Neven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855859/
https://www.ncbi.nlm.nih.gov/pubmed/36671530
http://dx.doi.org/10.3390/biom13010145
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author Perkovic, Matea Nikolac
Jaganjac, Morana
Milkovic, Lidija
Horvat, Tea
Rojo, David
Zarkovic, Kamelija
Ćorić, Marijana
Hudolin, Tvrtko
Waeg, Georg
Orehovec, Biserka
Zarkovic, Neven
author_facet Perkovic, Matea Nikolac
Jaganjac, Morana
Milkovic, Lidija
Horvat, Tea
Rojo, David
Zarkovic, Kamelija
Ćorić, Marijana
Hudolin, Tvrtko
Waeg, Georg
Orehovec, Biserka
Zarkovic, Neven
author_sort Perkovic, Matea Nikolac
collection PubMed
description An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody. Plasma samples of the same patients and samples of the healthy controls were also analyzed for the presence of 4-HNE-protein adducts, followed by metabolic profiling using LC-ESI-QTOF-MS and GC-EI-Q-MS. Finally, the analysis of the metabolic pathways affected by 4-HNE was performed. The obtained results revealed the absence of 4-HNE-protein adducts in prostate carcinoma tissue but increased 4-HNE-protein levels in the plasma of these patients. Metabolomics revealed a positive association of different long-chain and medium-chain fatty acids with the presence of prostate cancer. Furthermore, while linoleic acid positively correlated with the levels of 4-HNE-protein adducts in the blood of healthy men, no correlation was obtained for cancer patients indicating altered lipid metabolism in this case. The metabolic pathway of unsaturated fatty acids biosynthesis emerged as significantly affected by 4-HNE. Overall, this is the first study linking 4-HNE adduction to plasma proteins with specific alterations in the plasma metabolome of prostate cancer patients. This study revealed that increased 4-HNE plasma protein adducts could modulate the unsaturated fatty acids biosynthesis pathway. It is yet to be determined if this is a direct result of 4-HNE or whether they are produced by the same underlying mechanisms. Further mechanistic studies are needed to grasp the biological significance of the observed changes in prostate cancer tumorigenesis.
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spelling pubmed-98558592023-01-21 Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer Perkovic, Matea Nikolac Jaganjac, Morana Milkovic, Lidija Horvat, Tea Rojo, David Zarkovic, Kamelija Ćorić, Marijana Hudolin, Tvrtko Waeg, Georg Orehovec, Biserka Zarkovic, Neven Biomolecules Article An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody. Plasma samples of the same patients and samples of the healthy controls were also analyzed for the presence of 4-HNE-protein adducts, followed by metabolic profiling using LC-ESI-QTOF-MS and GC-EI-Q-MS. Finally, the analysis of the metabolic pathways affected by 4-HNE was performed. The obtained results revealed the absence of 4-HNE-protein adducts in prostate carcinoma tissue but increased 4-HNE-protein levels in the plasma of these patients. Metabolomics revealed a positive association of different long-chain and medium-chain fatty acids with the presence of prostate cancer. Furthermore, while linoleic acid positively correlated with the levels of 4-HNE-protein adducts in the blood of healthy men, no correlation was obtained for cancer patients indicating altered lipid metabolism in this case. The metabolic pathway of unsaturated fatty acids biosynthesis emerged as significantly affected by 4-HNE. Overall, this is the first study linking 4-HNE adduction to plasma proteins with specific alterations in the plasma metabolome of prostate cancer patients. This study revealed that increased 4-HNE plasma protein adducts could modulate the unsaturated fatty acids biosynthesis pathway. It is yet to be determined if this is a direct result of 4-HNE or whether they are produced by the same underlying mechanisms. Further mechanistic studies are needed to grasp the biological significance of the observed changes in prostate cancer tumorigenesis. MDPI 2023-01-10 /pmc/articles/PMC9855859/ /pubmed/36671530 http://dx.doi.org/10.3390/biom13010145 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Perkovic, Matea Nikolac
Jaganjac, Morana
Milkovic, Lidija
Horvat, Tea
Rojo, David
Zarkovic, Kamelija
Ćorić, Marijana
Hudolin, Tvrtko
Waeg, Georg
Orehovec, Biserka
Zarkovic, Neven
Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer
title Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer
title_full Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer
title_fullStr Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer
title_full_unstemmed Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer
title_short Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer
title_sort relationship between 4-hydroxynonenal (4-hne) as systemic biomarker of lipid peroxidation and metabolomic profiling of patients with prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855859/
https://www.ncbi.nlm.nih.gov/pubmed/36671530
http://dx.doi.org/10.3390/biom13010145
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