Kim Yong-Dae, Lantz-McPeak Susan M, Ali Syed F, Kleinman Michael T, Choi Young-Sook, Kim Heon
Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Neurochemistry Laboratory, Division of Neurotoxicology, National Center of Toxicological Research/Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, United States.
Environ Toxicol Pharmacol. 2014 May;37(3):954-9. doi: 10.1016/j.etap.2014.03.008. Epub 2014 Mar 22.
A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases, chemicals, and particles. Recent evidence suggests that exposure to air pollution can increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroinflammation and oxidative stress that may trigger neurodegenerative diseases, such as Parkinson's disease. The specific aim of this study was to determine whether ultrafine diesel exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs of 200 nm or smaller, cell viability, ROS and nitric oxide (NO(2)) generation, and levels of dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure (2.4 fold increase compared to control at 200 μg/mL). NO(2) levels were also dose-dependently increased after DEP exposure. Although not in a dose-dependent manner, upon DEP exposure, intracellular DA levels were increased while DOPAC and HVA levels decreased when compared to control. Results suggest that ultrafine DEPs lead to dopamine accumulation in the cytoplasm of PC-12 cells, possibly contributing to ROS formation. Further studies are warranted to elucidate this mechanism.
城市空气污染的一个主要成分是柴油废气,它是由气体、化学物质和颗粒组成的复杂混合物。最近的证据表明,暴露于空气污染中会增加致命中风的风险,导致脑血管损伤,并引发可能触发神经退行性疾病(如帕金森病)的神经炎症和氧化应激。本研究的具体目的是确定超细柴油废气颗粒(DEPs),即柴油发动机废气中的颗粒成分,是否能在PC-12细胞中诱导氧化应激并影响多巴胺代谢。在暴露于200纳米或更小的DEPs 24小时后,评估细胞活力、活性氧(ROS)和一氧化氮(NO₂)的生成,以及多巴胺(DA)及其代谢产物(二羟基苯乙酸(DOPAC)和高香草酸(HVA))的水平。结果表明,DEP暴露后细胞活力没有显著变化。然而,DEP暴露后ROS呈现出显著的剂量依赖性变化(在200μg/mL时与对照组相比增加了2.4倍)。DEP暴露后NO₂水平也呈剂量依赖性增加。与对照组相比,DEP暴露后细胞内DA水平增加,而DOPAC和HVA水平降低,尽管不是呈剂量依赖性。结果表明,超细DEPs导致PC-12细胞细胞质中多巴胺积累,可能有助于ROS的形成。有必要进行进一步研究以阐明这一机制。