Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients
Samo za registrovane korisnike
2014
Autori
Lukić, IvaMitić, Miloš
Đorđević, Jelena D.
Tatalović, Nikola R.
Božović, Natalija
Soldatovic, Ivan
Mihaljević, Marina
Pavlović, Zorana
Radojčić, Marija
Marić, Nađa P.
Adžić, Miroslav
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected... by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Basel
Ključne reči:
Major depressive disorder / Nuclear factor (erythroid-derived 2)-like 2 / Nuclear factor-kappa B / Antioxidative enzymesIzvor:
Neuropsychobiology, 2014, 70, 1, 1-9Finansiranje / projekti:
- Definisanje klastera molekulskih biomarkera za poboljšanu dijagnostiku i terapiju poremećaja raspoloženja (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41029)
DOI: 10.1159/000362841
ISSN: 0302-282X; 1423-0224
PubMed: 25170744
WoS: 000342887600001
Scopus: 2-s2.0-84906605867
Institucija/grupa
VinčaTY - JOUR AU - Lukić, Iva AU - Mitić, Miloš AU - Đorđević, Jelena D. AU - Tatalović, Nikola R. AU - Božović, Natalija AU - Soldatovic, Ivan AU - Mihaljević, Marina AU - Pavlović, Zorana AU - Radojčić, Marija AU - Marić, Nađa P. AU - Adžić, Miroslav PY - 2014 UR - https://vinar.vin.bg.ac.rs/handle/123456789/148 AB - Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Basel T2 - Neuropsychobiology T1 - Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients VL - 70 IS - 1 SP - 1 EP - 9 DO - 10.1159/000362841 ER -
@article{ author = "Lukić, Iva and Mitić, Miloš and Đorđević, Jelena D. and Tatalović, Nikola R. and Božović, Natalija and Soldatovic, Ivan and Mihaljević, Marina and Pavlović, Zorana and Radojčić, Marija and Marić, Nađa P. and Adžić, Miroslav", year = "2014", abstract = "Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Basel", journal = "Neuropsychobiology", title = "Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients", volume = "70", number = "1", pages = "1-9", doi = "10.1159/000362841" }
Lukić, I., Mitić, M., Đorđević, J. D., Tatalović, N. R., Božović, N., Soldatovic, I., Mihaljević, M., Pavlović, Z., Radojčić, M., Marić, N. P.,& Adžić, M.. (2014). Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients. in Neuropsychobiology, 70(1), 1-9. https://doi.org/10.1159/000362841
Lukić I, Mitić M, Đorđević JD, Tatalović NR, Božović N, Soldatovic I, Mihaljević M, Pavlović Z, Radojčić M, Marić NP, Adžić M. Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients. in Neuropsychobiology. 2014;70(1):1-9. doi:10.1159/000362841 .
Lukić, Iva, Mitić, Miloš, Đorđević, Jelena D., Tatalović, Nikola R., Božović, Natalija, Soldatovic, Ivan, Mihaljević, Marina, Pavlović, Zorana, Radojčić, Marija, Marić, Nađa P., Adžić, Miroslav, "Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients" in Neuropsychobiology, 70, no. 1 (2014):1-9, https://doi.org/10.1159/000362841 . .