e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 7 ( 2 0 1 4 ) 954–959
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/etap
Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells Yong-Dae Kim a,∗ , Susan M. Lantz-McPeak b , Syed F. Ali b,∗∗ , Michael T. Kleinman c , Young-Sook Choi a , Heon Kim a a
Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea b Neurochemistry Laboratory, Division of Neurotoxicology, National Center of Toxicological Research/Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, United States c Department of Medicine, University of California at Irvine, 19182 Jamboree Rd. FRF 100, Irvine, CA, United States
a r t i c l e
i n f o
a b s t r a c t
Article history:
A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases,
Received 10 November 2013
chemicals, and particles. Recent evidence suggests that exposure to air pollution can
Received in revised form
increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroin-
12 March 2014
flammation and oxidative stress that may trigger neurodegenerative diseases, such as
Accepted 13 March 2014
Parkinson’s disease. The specific aim of this study was to determine whether ultrafine diesel
Available online 22 March 2014
exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce
Keywords:
of 200 nm or smaller, cell viability, ROS and nitric oxide (NO2 ) generation, and levels of
Diesel exhaust particles
dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic
oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs
Oxidative stress
acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by
Dopamine
DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure
PC-12 cells
(2.4 fold increase compared to control at 200 g/mL). NO2 levels were also dose-dependently
Neurotoxicity
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. © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
Abbreviations: DEPs, diesel exhaust particles; DOPAC, dihydroxyphenylacetic acid; HVA, homovanillic acid; PM, particulate matter; DA, dopamine; HPLC, high performance liquid chromatography; PAHs, polycyclic aromatic hydrocarbons. ∗ Corresponding author. Tel.: +82 43 261 2845; fax: +82 43 274 2965. ∗∗ Corresponding author. Tel.: +1 870 543 7123; fax: +1 870 543 7745. E-mail addresses: [email protected] (Y.-D. Kim), [email protected] (S.F. Ali). http://dx.doi.org/10.1016/j.etap.2014.03.008 1382-6689/© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/3.0/).
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 7 ( 2 0 1 4 ) 954–959
1.
Introduction
Particulate matter (PM) is a main constituent of urban air pollution and may be associated with increased prevalence of respiratory disease and cardiovascular disease, related with increase in death rate (Pope et al., 2002; Brook et al., 2004). Diesel exhaust particles (DEPs) consist of several hundreds of organic and inorganic particulate and gases. According to their size, PM is divided into the following categories: ultrafine (
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/etap
Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells Yong-Dae Kim a,∗ , Susan M. Lantz-McPeak b , Syed F. Ali b,∗∗ , Michael T. Kleinman c , Young-Sook Choi a , Heon Kim a a
Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea b Neurochemistry Laboratory, Division of Neurotoxicology, National Center of Toxicological Research/Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, United States c Department of Medicine, University of California at Irvine, 19182 Jamboree Rd. FRF 100, Irvine, CA, United States
a r t i c l e
i n f o
a b s t r a c t
Article history:
A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases,
Received 10 November 2013
chemicals, and particles. Recent evidence suggests that exposure to air pollution can
Received in revised form
increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroin-
12 March 2014
flammation and oxidative stress that may trigger neurodegenerative diseases, such as
Accepted 13 March 2014
Parkinson’s disease. The specific aim of this study was to determine whether ultrafine diesel
Available online 22 March 2014
exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce
Keywords:
of 200 nm or smaller, cell viability, ROS and nitric oxide (NO2 ) generation, and levels of
Diesel exhaust particles
dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic
oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs
Oxidative stress
acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by
Dopamine
DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure
PC-12 cells
(2.4 fold increase compared to control at 200 g/mL). NO2 levels were also dose-dependently
Neurotoxicity
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. © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
Abbreviations: DEPs, diesel exhaust particles; DOPAC, dihydroxyphenylacetic acid; HVA, homovanillic acid; PM, particulate matter; DA, dopamine; HPLC, high performance liquid chromatography; PAHs, polycyclic aromatic hydrocarbons. ∗ Corresponding author. Tel.: +82 43 261 2845; fax: +82 43 274 2965. ∗∗ Corresponding author. Tel.: +1 870 543 7123; fax: +1 870 543 7745. E-mail addresses: [email protected] (Y.-D. Kim), [email protected] (S.F. Ali). http://dx.doi.org/10.1016/j.etap.2014.03.008 1382-6689/© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/3.0/).
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 7 ( 2 0 1 4 ) 954–959
1.
Introduction
Particulate matter (PM) is a main constituent of urban air pollution and may be associated with increased prevalence of respiratory disease and cardiovascular disease, related with increase in death rate (Pope et al., 2002; Brook et al., 2004). Diesel exhaust particles (DEPs) consist of several hundreds of organic and inorganic particulate and gases. According to their size, PM is divided into the following categories: ultrafine (
