Objective: The objective of this study was to determine the potential neurotoxicity of fine particulate matter (FPM) and the neuroprotective properties of nicotine in the pathogenesis of Parkinson’s disease (PD). In addition, we aimed to investigate whether nicotine protects against FPM-induced toxicity in the in vitro model of PD.
Background: Exposure to FPM has been considered as a potential risk factor, whereas cigarette smoking as a protective factor for PD. However, whether and how FPM alone and in combination with nicotine affect the pathogenesis of PD remains unclear.
Method: As an in vitro model of PD, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity model in SH-SY5Y cells was adapted. We measured cell viability using an MTT assay. The cell-permeant fluorescent probe DCFH-DA was used to quantify intracellular reactive oxygen species (ROS) levels and TUNEL assay analysis was used to investigate the numbers of apoptotic nuclei. The levels of mitochondria-associated apoptotic signaling proteins were analyzed by Western blotting.
Results: In SH-SY5Y cells, FPM at the concentration of 40μg/mL caused significant loss of cell viability. Nontoxic doses of FPM (5,10, and 20μg/mL) and MPTP (400μM) induced synergistic toxicity. The levels of ROS and mitochondrial apoptotic signaling proteins were significantly increased by FPM in the MPTP-treated SH-SY5Y cells. Pretreatment with nicotine reversed the MPTP-induced cell death, the generation of ROS, and mitochondrial apoptotic signaling proteins. However, nicotine did not attenuate the neurotoxicity induced by co-treatment of FPM and MPTP in SH-SY5Y cells.
Conclusion: FPM and MPTP worked in synergy to enhance oxidative stress and mitochondrial apoptotic pathway, leading to dopaminergic neuronal cell death. Nicotine protected against MPTP-induced neurotoxicity but failed to protect against FPM-induced synergistic toxicity in the MPTP-PD model. Mitochondria might act a crucial role in these processes. These findings provide an experimental basis for the pathogenesis of PD aggravated by exposure to FPM and protected by cigarette smoking. The aggravating effects of FPM appear to be more powerful than the protective effects of nicotine in the pathogenesis of PD.
To cite this abstract in AMA style:YJ. Jung, H. Choi, E. Oh. Effects of fine particulate matter and cigarette smoking on MPTP-induced dopaminergic neuronal cell death: Implication for Parkinson’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/effects-of-fine-particulate-matter-and-cigarette-smoking-on-mptp-induced-dopaminergic-neuronal-cell-death-implication-for-parkinsons-disease/. Accessed December 5, 2023.
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