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Oxidative and nitrosative stress in myeloproliferative neoplasms: the impact on the AKT/mTOR signaling pathway

Authorized Users Only
2018
Authors
Đikić, Dragoslava
Marković, Dragana
Bogdanović, Andrija
Mitrović-Ajtić, Olivera
Subotički, Tijana
Diklić, Miloš
Beleslin-Čokić, Bojana
Bjelica, Sunčica
Kovačić, Marijana
Čokić, Vladan
Article (Published version)
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Abstract
Purpose: A common feature of malignancies is increased reactive oxygen species (ROS) and reactive nitrogen species (RNS). We analyzed the influence of oxidative and nitrosative stress on the activation of AKT/mTOR signaling pathway in myeloproliferative neoplasms (MPN). Methods: Oxidative stress-induced gene expression in circulatory CD34(+) cells of MPN patients was studied by microarray analysis. Biomarkers of oxidative and nitrosative stress were determined using spectrophotometry in plasma and erythrocyte lysate. The levels of nitrotyrosine, inducible NO synthase (iNOS) and AKT/mTOR/p70S6K phosphorylation were determined by immunocytochemistry and immunoblotting in granulocytes of MPN patients. Results: Antioxidants superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPx1) gene expression were increased in circulatory CD34(+) cells, while SODI and GPx enzymes were reduced in the erythrocytes of MPN. Plasma malonyl-dialdehyde and protein carbonyl levels were elevated in MPN.... The total antioxidant capacity in plasma and erythrocyte catalase (CT) activities was the most prominent in primary myelofibrosis (PMF) with JAK2V617F heterozygosity. The total nitrite/ nitrate (NOx) level was augmented in the plasma of PMF patients (p lt 0.001), while nitrotyrosine and iNOS were generally increased in the granulocytes of MPN patients. Activation of AKT/m TOR signaling was the most significant in PMF (p lt 0.01), but demonstrated JAK2V617F dependence and consequent p70S6K phosphorylation in the granulocytes of essential thrombocytemia (ET) and polycythemia vera (PV) patients. Hydrogen peroxide stimulated mTOR pathway, iNOS and nitrotyrosine quantities, the last one prevented by the antioxidant nacetyl-cysteine (NAC) in the granulocytes of MPN. Conclusion: Our study showed increased levels of oxidative and nitrosative stress parameters in MPN with JAK2V617F dependence. The ROS enhanced the constitutive activation of AKT/mTOR signaling and nitrosative parameters in MPN.

Keywords:
AKT/mTOR signaling / myeloproliferative neoplasm / nitrosative stress / oxidative stress
Source:
Journal of BUON, 2018, 23, 5, 1481-1491
Publisher:
  • Balkan Union of Oncology (B.U.ON.)
Funding / projects:
  • The pathogenetic mechanism in hematological malignancies (RS-175053)

ISSN: 1107-0625

PubMed: 30570876

WoS: 000443737600037

[ Google Scholar ]
6
Handle
https://hdl.handle.net/21.15107/rcub_rimi_836
URI
http://rimi.imi.bg.ac.rs/handle/123456789/836
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
Institut za medicinska istraživanja
TY  - JOUR
AU  - Đikić, Dragoslava
AU  - Marković, Dragana
AU  - Bogdanović, Andrija
AU  - Mitrović-Ajtić, Olivera
AU  - Subotički, Tijana
AU  - Diklić, Miloš
AU  - Beleslin-Čokić, Bojana
AU  - Bjelica, Sunčica
AU  - Kovačić, Marijana
AU  - Čokić, Vladan
PY  - 2018
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/836
AB  - Purpose: A common feature of malignancies is increased reactive oxygen species (ROS) and reactive nitrogen species (RNS). We analyzed the influence of oxidative and nitrosative stress on the activation of AKT/mTOR signaling pathway in myeloproliferative neoplasms (MPN). Methods: Oxidative stress-induced gene expression in circulatory CD34(+) cells of MPN patients was studied by microarray analysis. Biomarkers of oxidative and nitrosative stress were determined using spectrophotometry in plasma and erythrocyte lysate. The levels of nitrotyrosine, inducible NO synthase (iNOS) and AKT/mTOR/p70S6K phosphorylation were determined by immunocytochemistry and immunoblotting in granulocytes of MPN patients. Results: Antioxidants superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPx1) gene expression were increased in circulatory CD34(+) cells, while SODI and GPx enzymes were reduced in the erythrocytes of MPN. Plasma malonyl-dialdehyde and protein carbonyl levels were elevated in MPN. The total antioxidant capacity in plasma and erythrocyte catalase (CT) activities was the most prominent in primary myelofibrosis (PMF) with JAK2V617F heterozygosity. The total nitrite/ nitrate (NOx) level was augmented in the plasma of PMF patients (p  lt 0.001), while nitrotyrosine and iNOS were generally increased in the granulocytes of MPN patients. Activation of AKT/m TOR signaling was the most significant in PMF (p lt 0.01), but demonstrated JAK2V617F dependence and consequent p70S6K phosphorylation in the granulocytes of essential thrombocytemia (ET) and polycythemia vera (PV) patients. Hydrogen peroxide stimulated mTOR pathway, iNOS and nitrotyrosine quantities, the last one prevented by the antioxidant nacetyl-cysteine (NAC) in the granulocytes of MPN. Conclusion: Our study showed increased levels of oxidative and nitrosative stress parameters in MPN with JAK2V617F dependence. The ROS enhanced the constitutive activation of AKT/mTOR signaling and nitrosative parameters in MPN.
PB  - Balkan Union of Oncology (B.U.ON.)
T2  - Journal of BUON
T1  - Oxidative and nitrosative stress in myeloproliferative neoplasms: the impact on the AKT/mTOR signaling pathway
EP  - 1491
IS  - 5
SP  - 1481
VL  - 23
UR  - conv_4378
ER  - 
@article{
author = "Đikić, Dragoslava and Marković, Dragana and Bogdanović, Andrija and Mitrović-Ajtić, Olivera and Subotički, Tijana and Diklić, Miloš and Beleslin-Čokić, Bojana and Bjelica, Sunčica and Kovačić, Marijana and Čokić, Vladan",
year = "2018",
abstract = "Purpose: A common feature of malignancies is increased reactive oxygen species (ROS) and reactive nitrogen species (RNS). We analyzed the influence of oxidative and nitrosative stress on the activation of AKT/mTOR signaling pathway in myeloproliferative neoplasms (MPN). Methods: Oxidative stress-induced gene expression in circulatory CD34(+) cells of MPN patients was studied by microarray analysis. Biomarkers of oxidative and nitrosative stress were determined using spectrophotometry in plasma and erythrocyte lysate. The levels of nitrotyrosine, inducible NO synthase (iNOS) and AKT/mTOR/p70S6K phosphorylation were determined by immunocytochemistry and immunoblotting in granulocytes of MPN patients. Results: Antioxidants superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPx1) gene expression were increased in circulatory CD34(+) cells, while SODI and GPx enzymes were reduced in the erythrocytes of MPN. Plasma malonyl-dialdehyde and protein carbonyl levels were elevated in MPN. The total antioxidant capacity in plasma and erythrocyte catalase (CT) activities was the most prominent in primary myelofibrosis (PMF) with JAK2V617F heterozygosity. The total nitrite/ nitrate (NOx) level was augmented in the plasma of PMF patients (p  lt 0.001), while nitrotyrosine and iNOS were generally increased in the granulocytes of MPN patients. Activation of AKT/m TOR signaling was the most significant in PMF (p lt 0.01), but demonstrated JAK2V617F dependence and consequent p70S6K phosphorylation in the granulocytes of essential thrombocytemia (ET) and polycythemia vera (PV) patients. Hydrogen peroxide stimulated mTOR pathway, iNOS and nitrotyrosine quantities, the last one prevented by the antioxidant nacetyl-cysteine (NAC) in the granulocytes of MPN. Conclusion: Our study showed increased levels of oxidative and nitrosative stress parameters in MPN with JAK2V617F dependence. The ROS enhanced the constitutive activation of AKT/mTOR signaling and nitrosative parameters in MPN.",
publisher = "Balkan Union of Oncology (B.U.ON.)",
journal = "Journal of BUON",
title = "Oxidative and nitrosative stress in myeloproliferative neoplasms: the impact on the AKT/mTOR signaling pathway",
pages = "1491-1481",
number = "5",
volume = "23",
url = "conv_4378"
}
Đikić, D., Marković, D., Bogdanović, A., Mitrović-Ajtić, O., Subotički, T., Diklić, M., Beleslin-Čokić, B., Bjelica, S., Kovačić, M.,& Čokić, V.. (2018). Oxidative and nitrosative stress in myeloproliferative neoplasms: the impact on the AKT/mTOR signaling pathway. in Journal of BUON
Balkan Union of Oncology (B.U.ON.)., 23(5), 1481-1491.
conv_4378
Đikić D, Marković D, Bogdanović A, Mitrović-Ajtić O, Subotički T, Diklić M, Beleslin-Čokić B, Bjelica S, Kovačić M, Čokić V. Oxidative and nitrosative stress in myeloproliferative neoplasms: the impact on the AKT/mTOR signaling pathway. in Journal of BUON. 2018;23(5):1481-1491.
conv_4378 .
Đikić, Dragoslava, Marković, Dragana, Bogdanović, Andrija, Mitrović-Ajtić, Olivera, Subotički, Tijana, Diklić, Miloš, Beleslin-Čokić, Bojana, Bjelica, Sunčica, Kovačić, Marijana, Čokić, Vladan, "Oxidative and nitrosative stress in myeloproliferative neoplasms: the impact on the AKT/mTOR signaling pathway" in Journal of BUON, 23, no. 5 (2018):1481-1491,
conv_4378 .

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