Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients
Само за регистроване кориснике
2015
Аутори
Lukić, IvaMitić, Miloš
Soldatovic, Ivan
Jovičić, Milica
Marić, Nađa
Radulović, Jelena
Adžić, Miroslav
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 difference...s 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.
Кључне речи:
Major depressive disorder / Glucocorticoid receptor / FKBP5 / GILZИзвор:
Journal of Molecular Neuroscience, 2015, 55, 4, 951-958Финансирање / пројекти:
- Дефинисање кластера молекулских биомаркера за побољшану дијагностику и терапију поремећаја расположења (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41029)
- NIH [1R21MH098793-01A1]
DOI: 10.1007/s12031-014-0451-z
ISSN: 0895-8696; 1559-1166
PubMed: 25355489
WoS: 000351090800016
Scopus: 2-s2.0-84924366622
Институција/група
VinčaTY - 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 . .