Assis-de-Lemos 2021 Biosci Rep

From Bioblast
Publications in the MiPMap
Assis-de-Lemos G, Monteiro J, Oliveira-Valença VM, Melo GA, Reis RAM, Rehen SK, Silveira MS, Galina A (2021) Dopamine signaling impairs ROS modulation by mitochondrial hexokinase in human neural progenitor cells. https://doi.org/10.1042/bsr20211191

Β» Biosci Rep 41:BSR20211191. PMID: 34821365 Open Access

Assis-de-Lemos Gabriela, Monteiro Jamila, Medeiros Oliveira-Valenca Viviane, Melo Guilherme A, de Melo Reis Ricoardo Augusto, Rehen Stevens Kastrup, Silveira Mariana S, Galina Antonio (2021) Biosci Rep

Abstract: Dopamine signaling has numerous roles during brain development. In addition, alterations in dopamine signaling may be also involved in the pathophysiology of psychiatric disorders. Neurodevelopment is modulated in multiple steps by reactive oxygen species (ROS), byproducts of oxidative metabolism which are signaling factors involved in proliferation, differentiation, and migration. Hexokinase (HK), when associated with the mitochondria (mt-HK), is a potent modulator of the generation of mitochondrial ROS in the brain. In this study we investigated whether dopamine could affect both the activity and redox function of mt-HK in human neural progenitor cells (NPCs). We found that dopamine signaling via D1R decreases mt-HK activity and impairs ROS modulation, which is followed by an expressive release of H2O2 and impairment in calcium handling by the mitochondria. Nevertheless, mitochondrial respiration is not affected, suggesting specificity for dopamine on mt-HK function. In neural stem cells (NSCs) derived from iPSCs of schizophrenia patients, mt-HK is unable to decrease mitochondrial ROS, in contrast to NSCs derived from healthy individuals. Our data point to mitochondrial hexokinase as a novel target of dopaminergic signaling, as well as a redox modulator in human neural progenitor cells, which may be relevant to the pathophysiology of neurodevelopmental disorders such as schizophrenia. β€’ Keywords: ROS, Dopamine, Mitochondria, mt-HK, Neurodevelopment β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: BR Rio de Janeiro Galina A, BR Rio de Janeiro Institute Biomedical Chemistry


Labels: MiParea: Respiration, Pharmacology;toxicology 


Organism: Human  Tissue;cell: Nervous system  Preparation: Intact cells 


Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k 

2021-11 

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