Clozapine suppresses NADPH oxidase activation, counteracts cytosolic H
Adipocyte differentiation
Clozapine
Mitochondrial ROS
Mitochondrial dysfunction
NADPH oxidase
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
21
07
2023
revised:
29
09
2023
accepted:
01
10
2023
medline:
30
10
2023
pubmed:
23
10
2023
entrez:
22
10
2023
Statut:
ppublish
Résumé
Long-term treatment of schizophrenia with clozapine (CLZ), an atypical antipsychotic drug, is associated with an increased incidence of metabolic disorders mediated by poorly understood mechanisms. We herein report that CLZ, while slowing down the morphological changes and lipid accumulation occurring during SW872 cell adipogenesis, also causes an early (day 3) inhibition of the expression/nuclear translocation of CAAT/enhancer-binding protein β and peroxisome proliferator-activated receptor γ. Under the same conditions, CLZ blunts NADPH oxidase-derived reactive oxygen species (ROS) by a dual mechanism involving enzyme inhibition and ROS scavenging. These effects were accompanied by hampered activation of the nuclear factor (erythroid-derived2)-like 2 (Nrf2)-dependent antioxidant responses compared to controls, and by an aggravated formation of mitochondrial superoxide. CLZ failed to exert ROS scavenging activities in the mitochondrial compartment but appeared to actively scavenge cytosolic H
Identifiants
pubmed: 37866162
pii: S2213-2317(23)00316-6
doi: 10.1016/j.redox.2023.102915
pmc: PMC10623370
pii:
doi:
Substances chimiques
NADPH Oxidases
EC 1.6.3.-
Reactive Oxygen Species
0
Clozapine
J60AR2IKIC
Hydrogen Peroxide
BBX060AN9V
Superoxides
11062-77-4
NF-E2-Related Factor 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102915Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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