Dopamine and Methamphetamine Differentially Affect Electron Transport Chain Complexes and Parkin in Rat Striatum: New Insight into Methamphetamine Neurotoxicity
| Autor: | Viktoriia Bazylianska, Akhil Sharma, Heli Chauhan, Bernard Schneider, Anna Moszczynska |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
electron transport chain complexes
QH301-705.5 Ubiquitin-Protein Ligases Neurotoxins amphetamine brain mitochondrial respiration nitric-oxide Buffers Models Biological Article Catalysis cytochrome-c Electron Transport Inorganic Chemistry methamphetamine dopamine parkin quality-control subcellular-localization Animals oxidative stress Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy dysfunction Organic Chemistry NADH Dehydrogenase General Medicine Corpus Striatum protein-degradation inhibition Mitochondria Rats Computer Science Applications Protein Subunits Chemistry Synaptosomes |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 363, p 363 (2022) International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 363 International Journal of Molecular Sciences |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Methamphetamine (METH) is a highly abused psychostimulant that is neurotoxic to dopaminergic (DAergic) nerve terminals in the striatum and increases the risk of developing Parkinson’s disease (PD). In vivo, METH-mediated DA release, followed by DA-mediated oxidative stress and mitochondrial dysfunction in pre- and postsynaptic neurons, mediates METH neurotoxicity. METH-triggered oxidative stress damages parkin, a neuroprotective protein involved in PD etiology via its involvement in the maintenance of mitochondria. It is not known whether METH itself contributes to mitochondrial dysfunction and whether parkin regulates complex I, an enzymatic complex downregulated in PD. To determine this, we separately assessed the effects of METH or DA alone on electron transport chain (ETC) complexes and the protein parkin in isolated striatal mitochondria. We show that METH decreases the levels of selected complex I, II, and III subunits (NDUFS3, SDHA, and UQCRC2, respectively), whereas DA decreases the levels only of the NDUFS3 subunit in our preparations. We also show that the selected subunits are not decreased in synaptosomal mitochondria under similar experimental conditions. Finally, we found that parkin overexpression does not influence the levels of the NDUFS3 subunit in rat striatum. The presented results indicate that METH itself is a factor promoting dysfunction of striatal mitochondria; therefore, it is a potential drug target against METH neurotoxicity. The observed decreases in ETC complex subunits suggest that DA and METH decrease activities of the ETC complexes via oxidative damage to their subunits and that synaptosomal mitochondria may be somewhat “resistant” to DA- and METH-induced disruption in mitochondrial ETC complexes than perikaryal mitochondria. The results also suggest that parkin does not regulate NDUFS3 turnover in rat striatum. |
| Databáze: | OpenAIRE |
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