Effects of particulate matter and nicotine for the MPP+-induced SH-SY5Y cells: Implication for Parkinson’s disease

Exposure to particulate matter (PM) has been considered a potential risk factor for various neurodegenerative diseases, whereas nicotine has protective effects on Parkinson’s disease (PD). However, it is still unclear whether or how PM alone and in combination with nicotine affects the pathogenesis of PD. We investigated the potential neurotoxicity of PM and the protective properties of nicotine in an in vitro PD model. A 1-methyl-4-phenylpyridimium (MPP+)-induced neurotoxicity model was established with SH-SY5Y cells. Cell viability and apoptosis were measured using MTT and TUNEL assays, respectively. Intracellular reactive oxygen species (ROS) levels were analyzed using the cell-permeant fluorescent probe DCFH-DA. We investigated mitochondrial apoptotic markers such as Bax, Bcl2, cytochrome C, and cleaved caspase-3 and analyzed their levels by Western blotting. SH-SY5Y cells exposed to PM and MPP+ exhibited significantly increased intracellular ROS and decreased cell viability with those exposed to PM alone. PM strikingly exacerbated MPP+-induced mitochondrial dysfunction, including an increase in the Bax/Bcl2 ratio and the release of cytochrome C and cleaved caspase-3. On the other hand, pretreatment of SH-SY5Y cells with nicotine reduced the MPP+-induced loss of cell viability and levels of intracellular ROS and mitochondrial apoptotic signaling proteins. However, pretreatment with nicotine did not prevent PM-induced toxicity in MPP+-treated SHSY5Y cells. PM and MPP+ synergistically increased ROS levels and mitochondrial apoptosis, which led to SH-SY5Y cell death. The protective effect of nicotine cannot rescue PM-induced synergistic neurotoxicity in the MPP+-induced PD model. Our findings verified the opposing roles of PM and nicotine in a model of PD pathogenesis. A large number of in vivo and in vitro studies would verify the roles of PM and nicotine in the future.