Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients
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Lukić, Iva
Mitić, Miloš

Đorđević, Jelena D.

Tatalović, Nikola R.

Božović, Natalija
Soldatovic, Ivan

Mihaljevic, Marina
Pavlović, Zorana
Radoičić, Marija B.

Maric, Nadja P.
Adžić, Miroslav

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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
Keywords:
Major depressive disorder / Nuclear factor (erythroid-derived 2)-like 2 / Nuclear factor-kappa B / Antioxidative enzymesSource:
Neuropsychobiology, 2014, 70, 1, 1-9Funding / projects:
- Defining a cluster of molecular biomarkers for improved diagnostics and therapy of mood disorders (RS-41029)
DOI: 10.1159/000362841
ISSN: 0302-282X; 1423-0224
PubMed: 25170744
WoS: 000342887600001
Scopus: 2-s2.0-84906605867
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VinčaTY - JOUR AU - Lukić, Iva AU - Mitić, Miloš AU - Đorđević, Jelena D. AU - Tatalović, Nikola R. AU - Božović, Natalija AU - Soldatovic, Ivan AU - Mihaljevic, Marina AU - Pavlović, Zorana AU - Radoičić, Marija B. AU - Maric, Nadja 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 Mihaljevic, Marina and Pavlović, Zorana and Radoičić, Marija B. and Maric, Nadja 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., Mihaljevic, M., Pavlović, Z., Radoičić, M. B., Maric, 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, Mihaljevic M, Pavlović Z, Radoičić MB, Maric 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, Mihaljevic, Marina, Pavlović, Zorana, Radoičić, Marija B., Maric, Nadja 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 . .