TY  - JOUR
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Soldatovic, Ivan
AU  - Jovičić, Milica
AU  - Marić, Nađa
AU  - Radulović, Jelena
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/445
AB  - We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.
T2  - Journal of Molecular Neuroscience
T1  - Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients
VL  - 55
IS  - 4
SP  - 951
EP  - 958
DO  - 10.1007/s12031-014-0451-z
ER  - 

@article{
author = "Lukić, Iva and Mitić, Miloš and Soldatovic, Ivan and Jovičić, Milica and Marić, Nađa and Radulović, Jelena and Adžić, Miroslav",
year = "2015",
abstract = "We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.",
journal = "Journal of Molecular Neuroscience",
title = "Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients",
volume = "55",
number = "4",
pages = "951-958",
doi = "10.1007/s12031-014-0451-z"
}

Lukić, I., Mitić, M., Soldatovic, I., Jovičić, M., Marić, N., Radulović, J.,& Adžić, M.. (2015). Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients. in Journal of Molecular Neuroscience, 55(4), 951-958.
https://doi.org/10.1007/s12031-014-0451-z

Lukić I, Mitić M, Soldatovic I, Jovičić M, Marić N, Radulović J, Adžić M. Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients. in Journal of Molecular Neuroscience. 2015;55(4):951-958.
doi:10.1007/s12031-014-0451-z .

Lukić, Iva, Mitić, Miloš, Soldatovic, Ivan, Jovičić, Milica, Marić, Nađa, Radulović, Jelena, Adžić, Miroslav, "Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients" in Journal of Molecular Neuroscience, 55, no. 4 (2015):951-958,
https://doi.org/10.1007/s12031-014-0451-z . .

TY  - JOUR
AU  - Jovičić, Milica
AU  - Marić, Nađa P.
AU  - Soldatovic, Ivan
AU  - Lukić, Iva
AU  - Andrić, Sanja
AU  - Mihaljević, Marina
AU  - Pavlović, Zorana
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/707
AB  - Objectives. To develop a structural equation model of negative affectivity (NA) that involves interaction of glucocorticoid receptor (GR) signaling, personality dimensions and recent stressful life events. Methods. Seventy participants -35 diagnosed with major depression and 35 healthy controls, were enrolled in the study. Morning plasma cortisol levels were determined by chemiluminescent immunometric assays. Molecular parameters (total nuclear and cytoplasmatic GR, nuclear GR phosphorylated at serine 211 (pGR-211) and at serine 226 (pGR-226) and cytoplasmic FKBP51) were analysed from peripheral blood lymphocytes by Western blot. NA, personality dimensions and stressful life events were assessed by self-report instruments. Results. GR signalling parameters had direct independent effect on measures of NA, with pGR-226 levels showing the strongest correlation, followed by FKBP51 and pGR-211 levels. Neuroticism and extraversion also demonstrated strong independent effect on NA, while recent stressful events did not predict NA directly, but demonstrated a significant effect on personality dimensions. Cortisol, total nuclear GR and total cytoplasmatic GR levels were excluded from the model due to non-significant correlations with NA. Conclusions. Negative affectivity is a transdiagnostic factor in vulnerability to affective disorders and possible therapeutic target. Molecular signature of negative affectivity should incorporate GR phosphorylation with other known biological underpinnings.
T2  - World Journal of Biological Psychiatry
T1  - The role of glucocorticoid receptor phosphorylation in the model of negative affective states
VL  - 16
IS  - 5
SP  - 301
EP  - 311
DO  - 10.3109/15622975.2014.1000375
ER  - 

@article{
author = "Jovičić, Milica and Marić, Nađa P. and Soldatovic, Ivan and Lukić, Iva and Andrić, Sanja and Mihaljević, Marina and Pavlović, Zorana and Mitić, Miloš and Adžić, Miroslav",
year = "2015",
abstract = "Objectives. To develop a structural equation model of negative affectivity (NA) that involves interaction of glucocorticoid receptor (GR) signaling, personality dimensions and recent stressful life events. Methods. Seventy participants -35 diagnosed with major depression and 35 healthy controls, were enrolled in the study. Morning plasma cortisol levels were determined by chemiluminescent immunometric assays. Molecular parameters (total nuclear and cytoplasmatic GR, nuclear GR phosphorylated at serine 211 (pGR-211) and at serine 226 (pGR-226) and cytoplasmic FKBP51) were analysed from peripheral blood lymphocytes by Western blot. NA, personality dimensions and stressful life events were assessed by self-report instruments. Results. GR signalling parameters had direct independent effect on measures of NA, with pGR-226 levels showing the strongest correlation, followed by FKBP51 and pGR-211 levels. Neuroticism and extraversion also demonstrated strong independent effect on NA, while recent stressful events did not predict NA directly, but demonstrated a significant effect on personality dimensions. Cortisol, total nuclear GR and total cytoplasmatic GR levels were excluded from the model due to non-significant correlations with NA. Conclusions. Negative affectivity is a transdiagnostic factor in vulnerability to affective disorders and possible therapeutic target. Molecular signature of negative affectivity should incorporate GR phosphorylation with other known biological underpinnings.",
journal = "World Journal of Biological Psychiatry",
title = "The role of glucocorticoid receptor phosphorylation in the model of negative affective states",
volume = "16",
number = "5",
pages = "301-311",
doi = "10.3109/15622975.2014.1000375"
}

Jovičić, M., Marić, N. P., Soldatovic, I., Lukić, I., Andrić, S., Mihaljević, M., Pavlović, Z., Mitić, M.,& Adžić, M.. (2015). The role of glucocorticoid receptor phosphorylation in the model of negative affective states. in World Journal of Biological Psychiatry, 16(5), 301-311.
https://doi.org/10.3109/15622975.2014.1000375

Jovičić M, Marić NP, Soldatovic I, Lukić I, Andrić S, Mihaljević M, Pavlović Z, Mitić M, Adžić M. The role of glucocorticoid receptor phosphorylation in the model of negative affective states. in World Journal of Biological Psychiatry. 2015;16(5):301-311.
doi:10.3109/15622975.2014.1000375 .

Jovičić, Milica, Marić, Nađa P., Soldatovic, Ivan, Lukić, Iva, Andrić, Sanja, Mihaljević, Marina, Pavlović, Zorana, Mitić, Miloš, Adžić, Miroslav, "The role of glucocorticoid receptor phosphorylation in the model of negative affective states" in World Journal of Biological Psychiatry, 16, no. 5 (2015):301-311,
https://doi.org/10.3109/15622975.2014.1000375 . .