Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells.
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.
Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea. Electronic address: ydkim@chungbuk.ac.kr.
Yong-Dae
YD
Kim
Neurochemistry Laboratory, Division of Neurotoxicology, National Center of Toxicological Research/Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, United States.
Susan M
SM
Lantz-McPeak
Neurochemistry Laboratory, Division of Neurotoxicology, National Center of Toxicological Research/Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, United States. Electronic address: syed.ali@fda.hhs.gov.
Syed F
SF
Ali
Department of Medicine, University of California at Irvine, 19182 Jamboree Rd. FRF 100, Irvine, CA, United States.
Michael T
MT
Kleinman
Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Young-Sook
YS
Choi
Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Heon
H
Kim
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010316:Particle Size; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D009566:Nitrates; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D007770:L-Lactate Dehydrogenase; D004298:Dopamine
Diesel exhaust particles; Dopamine; Neurotoxicity; Oxidative stress; PC-12 cells