Lactoferrin Protects Against Rotenone-Induced Toxicity in Dopaminergic SH-SY5Y Cells through the Modulation of Apoptotic-Associated Pathways.

Autor: Yong SJ; Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor Darul Ehsan, 47500, Bandar Sunway, Malaysia., Veerakumarasivam A; Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor Darul Ehsan, 47500, Bandar Sunway, Malaysia., Teoh SL; Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000, Kuala Lumpur, Malaysia., Lim WL; Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor Darul Ehsan, 47500, Bandar Sunway, Malaysia. weilingl@sunway.edu.my., Chew J; Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor Darul Ehsan, 47500, Bandar Sunway, Malaysia. jacttyc@sunway.edu.my.
Jazyk: angličtina
Zdroj: Journal of molecular neuroscience : MN [J Mol Neurosci] 2024 Sep 19; Vol. 74 (4), pp. 88. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1007/s12031-024-02267-7
Abstrakt: Parkinson's disease (PD) is a common motor neurodegenerative disease that still lacks effective therapeutic options. Previous studies have reported that lactoferrin exhibited neuroprotective effects in cellular and animal models of PD, typically induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP + ) synthetic toxin. However, the neuroprotective capacity of lactoferrin in the rotenone-induced cellular model of PD remains relatively less established. Unlike MPTP/MPP + , rotenone is a naturally occurring environmental toxin known to induce chronic toxicity and increase the risk of PD in humans. In this study, we constructed a cellular model of PD by differentiating SH-SY5Y neuroblastoma cells with retinoic acid into mature dopaminergic neurons with increased β-tubulin III and tyrosine hydroxylase expression, followed by 24 h of rotenone exposure. Using this cellular model of PD, we showed that lactoferrin (1-10 µg/ml) pre-treatment for 48 h decreased loss of cell viability, mitochondrial membrane potential impairment, reactive oxygen species generation and pro-apoptotic activities (pan-caspase activation and nuclear condensation) in cells exposed to rotenone (1 and 5 µM) using biochemical assays, Hoechst 33342 staining and immunocytochemical techniques. We further demonstrated that 48 h of lactoferrin (10 µg/ml) pre-treatment decreased Bax:Bcl2 ratio and p42/44 mitogen-activated protein kinase expression but increased pAkt expression in 5 µM rotenone-exposed cells. Our study demonstrates that lactoferrin neuroprotective capacity is present in the rotenone-induced cellular model of PD, further supporting lactoferrin as a potential PD therapeutic that warrants further studies.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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