The Oxidative Pathway to Dopamine-Protein Conjugates and Their Pro-Oxidant Activities: Implications for the Neurodegeneration of Parkinson's Disease.
Kazumasa WakamatsuKenta NakaoHitomi TanakaYuki KitahoriYui TanakaMakoto OjikaShosuke ItoPublished in: International journal of molecular sciences (2019)
Neuromelanin (NM) is a dark brown pigment found in dopaminergic neurons of the substantia nigra (SN) and in norepinephrinergic neurons of the locus coeruleus (LC). Although NM is thought to be involved in the etiology of Parkinson's disease (PD) because its content decreases in neurodegenerative diseases such as PD, details are still unknown. In this study, we characterized the biosynthetic pathway of the oxidation of dopamine (DA) by tyrosinase in the presence of thiol peptides and proteins using spectroscopic and high-performance liquid chromatography (HPLC) methods and we assessed the binding of DA via cysteine residues in proteins by oxidation catalyzed by redox-active metal ions. To examine whether the protein-bound DA conjugates exhibit pro-oxidant activities, we measured the depletion of glutathione (GSH) with the concomitant production of hydrogen peroxide. The results suggest that the fate of protein-bound DA conjugates depends on the structural features of the proteins and that DA-protein conjugates produced in the brain possess pro-oxidant activities, which may cause neurodegeneration due to the generation of reactive oxygen species (ROS) and the depletion of antioxidants.
Keyphrases
- hydrogen peroxide
- high performance liquid chromatography
- anti inflammatory
- simultaneous determination
- reactive oxygen species
- amino acid
- mass spectrometry
- protein protein
- binding protein
- tandem mass spectrometry
- cancer therapy
- nitric oxide
- solid phase extraction
- ms ms
- photodynamic therapy
- cell death
- multiple sclerosis
- quantum dots
- metabolic syndrome
- molecular docking
- drug delivery
- small molecule
- uric acid
- fluorescent probe
- white matter
- resting state
- spinal cord injury
- functional connectivity
- liquid chromatography
- single molecule
- molecular dynamics simulations