Blood and brain protein levels of ubiquitin-conjugating enzyme E2K (UBE2K) are elevated in individuals with schizophrenia.

J Psychiatr Res

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Parkville, VIC, Australia; The Cooperative Research Centre (CRC) for Mental Health, Victoria, Australia; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Published: June 2019

A number of recent studies have suggested the ubiquitin proteasome system (UPS) in schizophrenia is dysfunctional. The purpose of this study was to investigate UBE2K, a ubiquitin-conjugating (E2) enzyme within the UPS that has been associated with psychosis symptom severity, in the blood and brain of individuals with schizophrenia. Whole blood and erythrocytes from 128 (71 treatment-resistant schizophrenia, 57 healthy controls) individuals as well as frozen dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) post-mortem samples from 74 (37 schizophrenia, 37 controls) individuals were obtained. UBE2K gene expression was assayed in whole blood and DLPFC samples, whereas protein levels were assayed in erythrocytes and OFC samples. Elevated levels of UBE2K mRNA were observed in whole blood of individuals with schizophrenia (p = 0.03) but not in the DLPFC, while protein levels were raised in erythrocytes and the OFC (p < 0.001 and p = 0.002 respectively). Findings were not better explained by age, smoking, clozapine plasma levels or duration of illness. Although blood and brain samples were derived from independent samples, our findings suggest peripheral protein levels of UBE2K may serve as a surrogate of brain levels and further supports the notion of UPS dysfunction in schizophrenia. Future studies to determine the pathophysiological effects of elevated UBE2K protein levels in the brain of those with schizophrenia are warranted.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2019.03.005DOI Listing

Publication Analysis

Top Keywords

protein levels
12
individuals schizophrenia
12
blood brain
8
ubiquitin-conjugating enzyme
8
controls individuals
8
erythrocytes ofc
8
schizophrenia
6
blood
5
individuals
5
brain protein
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!