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Lipidomic and metallomic alteration of Caenorhabditis elegans after acute and chronic manganese, iron and zinc exposure with link to neurodegenerative disorders.
J. Proteome Res. 22, 837–850 (2023)
Parkinson's disease (PD) progresses with the loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain. The superior mechanisms and the cause of this specific localized neurodegeneration is currently unknown. However, experimental evidence indicates a link between PD progression and reactive oxygen species with imbalanced metal homeostasis. Wild-type Caenorhabditis elegans exposed to redox-active metals was used as the model organism to study cellular response to imbalanced metal homeostasis linked to neurodegenerative diseases. Using modern hyphenated techniques such as capillary electrophoresis coupled to inductively coupled plasma mass spectrometry and ultrahigh-performance liquid chromatography mass spectrometry, alterations in the lipidome and metallome were determined in vivo. In contrast to iron, most of the absorbed zinc and manganese were loosely bound. We observed changes in the phospholipid composition for acute iron and manganese exposures, as well as chronic zinc exposure. Furthermore, we focused on the mitochondrial membrane alteration due to its importance in neuronal function. However, significant changes in the inner mitochondrial membrane by determination of cardiolipin species could only be observed for acute iron exposure. These results indicate different intracellular sites of local ROS generation, depending on the redox active metal. Our study combines metallomic and lipidomic alterations as the cause and consequence to enlighten intracellular mechanisms in vivo, associated with PD progression. The mass spectrometry raw data have been deposited to the MassIVE database (https://massive.ucsd.edu) with the identifier MSV000090796 and 10.25345/C51J97C8F.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
C. Elegans ; Cardiolipins ; Labile Iron Pool ; Labile Metal Pool ; Lipidomics ; Metal Treatment ; Neurodegeneration ; Oxidative Stress; Liquid-chromatography; Parkinsons-disease; Cytochrome-c; Dopamine; Toxicity; Involvement; Glutathione; Ferritin; Brain; Cells
ISSN (print) / ISBN
1535-3893
e-ISSN
1535-3907
Journal
Journal of Proteome Research
Quellenangaben
Volume: 22,
Issue: 3,
Pages: 837–850
Publisher
American Chemical Society (ACS)
Publishing Place
1155 16th St, Nw, Washington, Dc 20036 Usa
Non-patent literature
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Reviewing status
Peer reviewed