Reference : Impairment of neuronal mitochondrial function by l-DOPA in the absence of oxygen-depe...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/47621
Impairment of neuronal mitochondrial function by l-DOPA in the absence of oxygen-dependent auto-oxidation and oxidative cell damage
English
Hörmann, Philipp [Department of Bioinformatics and Biochemistry, Technische Universität Braunschweig, Braunschweig, Germany]
Delcambre, Sylvie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology >]
Hanke, Jasmin [Department of Bioinformatics and Biochemistry, Technische Universität Braunschweig, Braunschweig, Germany]
Geffers, Robert [Genome Analytics, Helmholtz-Center for Infection Research, Braunschweig, Germany]
Leist, Marcel [In Vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany]
Hiller, Karsten [Department of Bioinformatics and Biochemistry, Technische Universität Braunschweig, Braunschweig, Germany]
28-Jun-2021
Cell Death Discovery
Nature
Yes (verified by ORBilu)
International
2058-7716
London
United Kingdom
[en] L-3,4-Dihydroxyphenylalanin (l-DOPA or levodopa) is currently the most used drug to treat symptoms of Parkinson’s disease (PD). After crossing the blood–brain barrier, it is enzymatically converted to dopamine by neuronal cells and restores depleted endogenous neurotransmitter levels. l-DOPA is prone to auto-oxidation and reactive intermediates of its degradation including reactive oxygen species (ROS) have been implicated in cellular damage. In this study, we investigated how oxygen tension effects l-DOPA stability. We applied oxygen tensions comparable to those in the mammalian brain and demonstrated that 2% oxygen almost completely stopped its auto-oxidation. l-DOPA even exerted a ROS scavenging function. Further mechanistic analysis indicated that l-DOPA reprogrammed mitochondrial metabolism and reduced oxidative phosphorylation, depolarized the mitochondrial membrane, induced reductive glutamine metabolism, and depleted the NADH pool. These results shed new light on the cellular effects of l-DOPA and its neuro-toxicity under physiological oxygen levels that are very distinct to normoxic in vitro conditions.
http://hdl.handle.net/10993/47621
10.1038/s41420-021-00547

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
Hoermann2021-Impairment of neuronal mitochondrial function by L-DOPA n the abscence of oxygen-dependent auto-oxidation and oxidative cell damage.pdfPublisher postprint2.31 MBView/Open

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.