Alcohol Triggers the Accumulation of Oxidatively Damaged Proteins in Neuronal Cells and Tissues

Mudyanselage, Anusha W.; Wijamunige, Buddhika C.; Kocoń, Artur; Turner, Ricky; McLean, Denise; Morentin, Benito; Callado, Luis F.; Carter, Wayne G.

Abstract

Alcohol is toxic to neurons and can trigger alcohol-related brain damage, neuronal loss, and cognitive decline. Neuronal cells may be vulnerable to alcohol toxicity and damage from oxidative stress after differentiation. To consider this further, the toxicity of alcohol to undifferentiated SH-SY5Y cells was compared with that of cells that had been acutely differentiated. Cells were exposed to alcohol over a concentration range of 0–200 mM for up to 24 h and alcohol effects on cell viability were evaluated via MTT and LDH assays. Effects on mitochondrial morphology were examined via transmission electron microscopy, and mitochondrial functionality was examined using measurements of ATP and the production of reactive oxygen species (ROS). Alcohol reduced cell viability and depleted ATP levels in a concentration- and exposure duration-dependent manner, with undifferentiated cells more vulnerable to toxicity. Alcohol exposure resulted in neurite retraction, altered mitochondrial morphology, and increased the levels of ROS in proportion to alcohol concentration; these peaked after 3 and 6 h exposures and were significantly higher in differentiated cells. Protein carbonyl content (PCC) lagged behind ROS production and peaked after 12 and 24 h, increasing in proportion to alcohol concentration, with higher levels in differentiated cells. Carbonylated proteins were characterised by their denatured molecular weights and overlapped with those from adult post-mortem brain tissue, with levels of PCC higher in alcoholic subjects than matched controls. Hence, alcohol can potentially trigger cell and tissue damage from oxidative stress and the accumulation of oxidatively damaged proteins.

Citation

Mudyanselage, A. W., Wijamunige, B. C., Kocoń, A., Turner, R., McLean, D., Morentin, B., Callado, L. F., & Carter, W. G. (2024). Alcohol Triggers the Accumulation of Oxidatively Damaged Proteins in Neuronal Cells and Tissues. Antioxidants, 13(5), Article 580. https://doi.org/10.3390/antiox13050580

• Journal Article Type: Article
• Acceptance Date: May 4, 2024
• Online Publication Date: May 8, 2024
• Publication Date: May 8, 2024
• Deposit Date: May 10, 2024
• Publicly Available Date: May 10, 2024
• Journal: Antioxidants
• Electronic ISSN: 2076-3921
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 5
• Article Number: 580
• DOI: https://doi.org/10.3390/antiox13050580
• Keywords: Alcohol; alcohol-related brain damage; developmental neurotoxicity; oxidative stress; protein carbonylation; reactive oxygen species
• Public URL: https://nottingham-repository.worktribe.com/output/34631297