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. Conclusion: 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.

An altered peripheral IL6 response in major depressive disorder

“…Our results suggest that MDD fibroblasts have a diminished IL6 response with the exception of NFKB1 and SOD2 induction. Our findings, in concordance with previous studies in MDD patients, support a role for nf κ b expression in MDD pathogenesis (Lukic et al, 2014; Pace et al, 2006). …”

Markers of Oxidative Stress and Neuroprogression in Depression Disorder

“…NF κ B itself increases oxidative stress in the organism and causes inflammatory reaction which can lead to neuroprogression [ 5 , 8 , 70 ]. Increased levels of NF κ B were observed in depressed patients [ 38 ].…”

“…Activity of antioxidant enzymes was found controversial in patients with depression. In some studies increased activities were detected but, on the other hand, several studies published mixed or negative results of enzymes activity in depression in comparison to healthy control groups ( Table 1 , Figure 1 ) [ 38 , 39 , 41 ]. The contradiction can be caused by small study sample, heterogeneity of patients' statuses, or variability in individual experiments [ 8 ].…”

Effect of sitagliptin on depression in male wistar rats

“…This finding was consistent with the studies performed by Galecki et al who did not find significantly different level of GPX in depressed patients. 21 Thus, our study showed that sitagliptin could alleviate depressive symptoms in male wistar rats using Forced Swim test. Based on the results obtained, there appears to be a role of DPP-4 inhibitors in depression, most probably by their anti-inflammatory and anti-oxidative properties.…”