Aroclor 1254-induced cytotoxicity in catecholaminergic CATH.a cells related to the inhibition of NO production.
The neuronal nitric oxide synthase (nNOS) specific inhibitor, 7-nitroindazole (7-NI), and the nitric oxide (NO) donor (S-nitroso-N-acetylpenicillarnine, SNAP) were used to study the role of NO in polychlorinated biphenyl (PCB: Aroclor 1254)-induced cytotoxicity in the immortalized dopaminergic cell line (CATH.a cells), derived from the central nervous system of mice. Treatment of the dopaminergic cells with various concentrations of Aroclor 1254 (0.5-10 microg/ml), a commercial PCB mixture, showed significant cytotoxicity as evaluated by lactate dehydrogenase (LDH) release and assessment of cell viability, depending on the concentration used. We also observed that Aroclor 1254 treatment reduced the level of nNOS expression. Furthermore, the cytotoxicity of Aroclor 1254 was augmented by 10 microM of 7-NI, which alone did not produce cytotoxicity, while it was protected by treatment with SNAP. Depending on the concentrations of Aroclor 1254 used, intracellular dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations were significantly decreased. Therefore, these results suggest that PCBs have the potential for dopaminergic neurotoxicity, which may be related with the PCBs-mediated alteration of NO production originating from nNOS at least in part.
Kang
Ju Hee
JH
Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 5 Nokbundong, Eunpyung-Gu, Seoul, South Korea.
Jeong
Wonhyung
W
Park
Younjoo
Y
Lee
Sung Yong
SY
Chung
Myeon Woo
MW
Lim
Hwa Kyung
HK
Park
In Sook
IS
Choi
Ki Hwan
KH
Chung
Soo Youn
SY
Kim
Dong Seop
DS
Park
Chang Shin
CS
Hwang
Onyou
O
Kim
Joo il
Ji
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D004298:Dopamine / Q000032:analysis*; D007191:Indazoles / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology
D007191:Indazoles; C110881:S-nitro-N-acetylpenicillamine; D015102:3,4-Dihydroxyphenylacetic Acid; D020111:Chlorodiphenyl (54% Chlorine); D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D010396:Penicillamine; C080122:7-nitroindazole; D004298:Dopamine