Cargando…

Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia

Dysregulation of the ubiquitin proteasome system (UPS) has been linked to schizophrenia but it is not clear if this dysregulation is detectable in both brain and blood. We examined free mono-ubiquitin, ubiquitinated proteins, catalytic ubiquitination, and proteasome activities in frozen postmortem O...

Descripción completa

Detalles Bibliográficos
Autores principales: Bousman, Chad A., Luza, Sandra, Mancuso, Serafino G., Kang, Dali, Opazo, Carlos M., Mostaid, Md. Shaki, Cropley, Vanessa, McGorry, Patrick, Shannon Weickert, Cynthia, Pantelis, Christos, Bush, Ashley I., Everall, Ian P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381171/
https://www.ncbi.nlm.nih.gov/pubmed/30783160
http://dx.doi.org/10.1038/s41598-019-38490-1
_version_ 1783396455643348992
author Bousman, Chad A.
Luza, Sandra
Mancuso, Serafino G.
Kang, Dali
Opazo, Carlos M.
Mostaid, Md. Shaki
Cropley, Vanessa
McGorry, Patrick
Shannon Weickert, Cynthia
Pantelis, Christos
Bush, Ashley I.
Everall, Ian P.
author_facet Bousman, Chad A.
Luza, Sandra
Mancuso, Serafino G.
Kang, Dali
Opazo, Carlos M.
Mostaid, Md. Shaki
Cropley, Vanessa
McGorry, Patrick
Shannon Weickert, Cynthia
Pantelis, Christos
Bush, Ashley I.
Everall, Ian P.
author_sort Bousman, Chad A.
collection PubMed
description Dysregulation of the ubiquitin proteasome system (UPS) has been linked to schizophrenia but it is not clear if this dysregulation is detectable in both brain and blood. We examined free mono-ubiquitin, ubiquitinated proteins, catalytic ubiquitination, and proteasome activities in frozen postmortem OFC tissue from 76 (38 schizophrenia, 38 control) matched individuals, as well as erythrocytes from 181 living participants, who comprised 30 individuals with recent onset schizophrenia (mean illness duration = 1 year), 63 individuals with ‘treatment-resistant’ schizophrenia (mean illness duration = 17 years), and 88 age-matched participants without major psychiatric illness. Ubiquitinated protein levels were elevated in postmortem OFC in schizophrenia compared to controls (p = <0.001, AUC = 74.2%). Similarly, individuals with ‘treatment-resistant’ schizophrenia had higher levels of ubiquitinated proteins in erythrocytes compared to those with recent onset schizophrenia (p < 0.001, AUC = 65.5%) and controls (p < 0.001, AUC = 69.4%). The results could not be better explained by changes in proteasome activity, demographic, medication, or tissue factors. Our results suggest that ubiquitinated protein formation may be abnormal in both the brain and erythrocytes of those with schizophrenia, particularly in the later stages or specific sub-groups of the illness. A derangement in protein ubiquitination may be linked to pathogenesis or neurotoxicity in schizophrenia, and its manifestation in the blood may have prognostic utility.
format Online
Article
Text
id pubmed-6381171
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63811712019-02-22 Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia Bousman, Chad A. Luza, Sandra Mancuso, Serafino G. Kang, Dali Opazo, Carlos M. Mostaid, Md. Shaki Cropley, Vanessa McGorry, Patrick Shannon Weickert, Cynthia Pantelis, Christos Bush, Ashley I. Everall, Ian P. Sci Rep Article Dysregulation of the ubiquitin proteasome system (UPS) has been linked to schizophrenia but it is not clear if this dysregulation is detectable in both brain and blood. We examined free mono-ubiquitin, ubiquitinated proteins, catalytic ubiquitination, and proteasome activities in frozen postmortem OFC tissue from 76 (38 schizophrenia, 38 control) matched individuals, as well as erythrocytes from 181 living participants, who comprised 30 individuals with recent onset schizophrenia (mean illness duration = 1 year), 63 individuals with ‘treatment-resistant’ schizophrenia (mean illness duration = 17 years), and 88 age-matched participants without major psychiatric illness. Ubiquitinated protein levels were elevated in postmortem OFC in schizophrenia compared to controls (p = <0.001, AUC = 74.2%). Similarly, individuals with ‘treatment-resistant’ schizophrenia had higher levels of ubiquitinated proteins in erythrocytes compared to those with recent onset schizophrenia (p < 0.001, AUC = 65.5%) and controls (p < 0.001, AUC = 69.4%). The results could not be better explained by changes in proteasome activity, demographic, medication, or tissue factors. Our results suggest that ubiquitinated protein formation may be abnormal in both the brain and erythrocytes of those with schizophrenia, particularly in the later stages or specific sub-groups of the illness. A derangement in protein ubiquitination may be linked to pathogenesis or neurotoxicity in schizophrenia, and its manifestation in the blood may have prognostic utility. Nature Publishing Group UK 2019-02-19 /pmc/articles/PMC6381171/ /pubmed/30783160 http://dx.doi.org/10.1038/s41598-019-38490-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bousman, Chad A.
Luza, Sandra
Mancuso, Serafino G.
Kang, Dali
Opazo, Carlos M.
Mostaid, Md. Shaki
Cropley, Vanessa
McGorry, Patrick
Shannon Weickert, Cynthia
Pantelis, Christos
Bush, Ashley I.
Everall, Ian P.
Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
title Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
title_full Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
title_fullStr Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
title_full_unstemmed Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
title_short Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
title_sort elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381171/
https://www.ncbi.nlm.nih.gov/pubmed/30783160
http://dx.doi.org/10.1038/s41598-019-38490-1
work_keys_str_mv AT bousmanchada elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT luzasandra elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT mancusoserafinog elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT kangdali elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT opazocarlosm elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT mostaidmdshaki elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT cropleyvanessa elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT mcgorrypatrick elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT shannonweickertcynthia elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT pantelischristos elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT bushashleyi elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia
AT everallianp elevatedubiquitinatedproteinsinbrainandbloodofindividualswithschizophrenia