Cargando…
Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia
Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the proliferation-rela...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961589/ https://www.ncbi.nlm.nih.gov/pubmed/35204748 http://dx.doi.org/10.3390/biom12020247 |
_version_ | 1784677629935222784 |
---|---|
author | Đikić, Dragoslava Bogdanović, Andrija Marković, Dragana Mitrović-Ajtić, Olivera Subotički, Tijana Diklić, Miloš Vukotić, Milica Dragojević, Teodora Živković, Emilija Santibanez, Juan F. Čokić, Vladan P. |
author_facet | Đikić, Dragoslava Bogdanović, Andrija Marković, Dragana Mitrović-Ajtić, Olivera Subotički, Tijana Diklić, Miloš Vukotić, Milica Dragojević, Teodora Živković, Emilija Santibanez, Juan F. Čokić, Vladan P. |
author_sort | Đikić, Dragoslava |
collection | PubMed |
description | Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the proliferation-related AKT/mTOR signaling pathway and the relationship with inflammatory factors in chronic myelogenous leukemia (CML). The activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase is reduced in erythrocytes while levels of the oxidative stress markers malondialdehyde and protein carbonyl are elevated in the plasma of patients with CML. In addition, nitrogen species (nitrotyrosine, iNOS, eNOS) and inflammation markers (IL-6, NFkB, and S100 protein) were increased in granulocytes of CML while anti-inflammatory levels of IL-10 were decreased in plasma. CML granulocytes exhibited greater resistance to cytotoxic H(2)O(2) activity compared to healthy subjects. Moreover, phosphorylation of the apoptotic p53 protein was reduced while the activity of the AKT/mTOR signaling pathway was increased, which was further enhanced by oxidative stress (H(2)O(2)) in granulocytes and erythroleukemic K562 cells. IL-6 caused oxidative stress and DNA damage that was mitigated using antioxidant or inhibition of inflammatory NFkB transcription factor in K562 cells. We demonstrated the presence of oxidative and nitrosative stress in CML, with the former mediated by AKT/mTOR signaling and stimulated by inflammation. |
format | Online Article Text |
id | pubmed-8961589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89615892022-03-30 Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia Đikić, Dragoslava Bogdanović, Andrija Marković, Dragana Mitrović-Ajtić, Olivera Subotički, Tijana Diklić, Miloš Vukotić, Milica Dragojević, Teodora Živković, Emilija Santibanez, Juan F. Čokić, Vladan P. Biomolecules Article Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the proliferation-related AKT/mTOR signaling pathway and the relationship with inflammatory factors in chronic myelogenous leukemia (CML). The activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase is reduced in erythrocytes while levels of the oxidative stress markers malondialdehyde and protein carbonyl are elevated in the plasma of patients with CML. In addition, nitrogen species (nitrotyrosine, iNOS, eNOS) and inflammation markers (IL-6, NFkB, and S100 protein) were increased in granulocytes of CML while anti-inflammatory levels of IL-10 were decreased in plasma. CML granulocytes exhibited greater resistance to cytotoxic H(2)O(2) activity compared to healthy subjects. Moreover, phosphorylation of the apoptotic p53 protein was reduced while the activity of the AKT/mTOR signaling pathway was increased, which was further enhanced by oxidative stress (H(2)O(2)) in granulocytes and erythroleukemic K562 cells. IL-6 caused oxidative stress and DNA damage that was mitigated using antioxidant or inhibition of inflammatory NFkB transcription factor in K562 cells. We demonstrated the presence of oxidative and nitrosative stress in CML, with the former mediated by AKT/mTOR signaling and stimulated by inflammation. MDPI 2022-02-03 /pmc/articles/PMC8961589/ /pubmed/35204748 http://dx.doi.org/10.3390/biom12020247 Text en © 2022 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 Đikić, Dragoslava Bogdanović, Andrija Marković, Dragana Mitrović-Ajtić, Olivera Subotički, Tijana Diklić, Miloš Vukotić, Milica Dragojević, Teodora Živković, Emilija Santibanez, Juan F. Čokić, Vladan P. Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia |
title | Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia |
title_full | Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia |
title_fullStr | Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia |
title_full_unstemmed | Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia |
title_short | Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia |
title_sort | inflammation promotes oxidative and nitrosative stress in chronic myelogenous leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961589/ https://www.ncbi.nlm.nih.gov/pubmed/35204748 http://dx.doi.org/10.3390/biom12020247 |
work_keys_str_mv | AT đikicdragoslava inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT bogdanovicandrija inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT markovicdragana inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT mitrovicajticolivera inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT subotickitijana inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT diklicmilos inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT vukoticmilica inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT dragojevicteodora inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT zivkovicemilija inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT santibanezjuanf inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia AT cokicvladanp inflammationpromotesoxidativeandnitrosativestressinchronicmyelogenousleukemia |