Τίτλος:
A longitudinal study of alterations of circulating DJ-1 and miR203a-3p in association to olanzapine medication in a sample of first episode patients with schizophrenia
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Among different proposed pathophysiological mechanisms, redox imbalance has been suggested to be a potential contributor in the pathogenesis of schizophrenia. DJ-1 is a redox-sensitive protein that has been shown to have neuroprotective function in the brain in Parkinson's disease and other neurodegenerative diseases. However, a role for DJ-1 in schizophrenia is unknown. Bioinformatic analysis suggested that microRNA (miR)-203a-3p could target the 3′ untranslated region (UTR) of DJ-1. In whole blood and blood-derived exosomes of 11 first episode antipsychotic naïve schizophrenia patients, DJ-1 protein and mRNA demonstrated decreased DJ-1 mRNA and protein and increased miR203a-3p levels compared to healthy controls. In whole blood, antipsychotic monotherapy with olanzapine for 6 weeks increased DJ-1 and attenuated miR203a-3p levels, whereas in blood derived exosomes, olanzapine returned DJ-1 and miR203a-3p to levels seen healthy controls. Consistent with this finding, we showed that human umbilical vein endothelial cells (HUVACs) transfected with a DJ-1–3′ UTR luciferase reporter construct displayed reduced gene expression when subjected to the oxidative stressor H2O2. Transfection of a miR203a-3p mimic into HUVACs reduced DJ-1–3 ‘UTR reporter gene expression, while transfection of an anti miR-203a-3p prevented the H2O2-induced downregulation of the reporter gene. We conclude that miR-203a-3p is an essential mediator of oxidative stress in schizophrenia via its ability to target the 3’ UTR of DJ-1 and antipsychotic monotherapy restores DJ-1 antioxidant levels by regulating miR203a-3p expression. miR-203a-3p and DJ-1 might represent attractive targets for the treatment of pathologies such as schizophrenia that has underlying oxidative stress. © 2021 Elsevier Ltd
Συγγραφείς:
Tsoporis, J.N.
Ektesabi, A.M.
Gupta, S.
Izhar, S.
Salpeas, V.
Rizos, I.K.
Kympouropoulos, S.P.
dos Santos, C.C.
Parker, T.G.
Rizos, E.
Περιοδικό:
Journal of Psychiatric Research
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
hydrogen peroxide; luciferase; messenger RNA; microRNA; microRNA 203a 3p; olanzapine; protein deglycase DJ-1; unclassified drug, 3' untranslated region; adult; Article; bioinformatics; clinical article; controlled study; down regulation; exosome; female; gene expression regulation; gene set enrichment analysis; genetic transfection; human; human cell; human tissue; longitudinal study; male; monotherapy; mRNA expression level; oxidative stress; pathogenesis; pathophysiology; Positive and Negative Syndrome Scale; protein blood level; protein expression level; reporter gene; schizophrenia; transcription initiation; umbilical vein endothelial cell; upregulation; young adult
DOI:
10.1016/j.jpsychires.2021.12.049
