title: Lymphocyte levels of redox-sensitive transcription factors and antioxidative enzymes as indicators of pro-oxidative state in depressive patients.
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-κB (NF-κB), 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-κB 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-κB. 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.
  
  
  CONCLUSIONS
  These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-κB) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients.
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, Belgrade, Serbia.
authors.forename: Iva
authors.initials: I
authors.lastname: Lukic
authors.forename: Milos
authors.initials: M
authors.lastname: Mitic
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
authors.forename: Nikola
authors.initials: N
authors.lastname: Tatalovic
authors.forename: Natalija
authors.initials: N
authors.lastname: Bozovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Soldatovic
authors.forename: Marina
authors.initials: M
authors.lastname: Mihaljevic
authors.forename: Zorana
authors.initials: Z
authors.lastname: Pavlovic
authors.forename: Marija B
authors.initials: MB
authors.lastname: Radojcic
authors.forename: Nadja P
authors.initials: NP
authors.lastname: Maric
authors.forename: Miroslav
authors.initials: M
authors.lastname: Adzic
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase; D003866:Depressive Disorder / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase