Association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells

The investigations were aimed to study the possible association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells, one among the most studied cell line in neurotoxicity studies. PC12 cells were subjected to receive an exposure of rotenone (10-6 to 10-4 M) for 24 and 48 hours....

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Bibliographic Details
Published in:Toxicology and industrial health 2010-09, Vol.26 (8), p.533-542
Main Authors: Siddiqui, MA, Kashyap, MP, Khanna, VK, Yadav, S., Al-Khedhairy, AA, Musarrat, J., Pant, AB
Format: Article
Language:English
Subjects:
Animals
Cytotoxicity
Dehydrogenases
Dopamine
Glutathione - metabolism
Insecticides - toxicity
L-Lactate Dehydrogenase - metabolism
Laboratories
Neurotoxicity
Oxidative stress
Parkinson's disease
PC12 Cells
Rats
Receptors, Dopamine D2 - metabolism
Rotenone - toxicity
Tetrazolium Salts - metabolism
Thiazoles - metabolism
Toxicity Tests
Toxicology
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Summary:The investigations were aimed to study the possible association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells, one among the most studied cell line in neurotoxicity studies. PC12 cells were subjected to receive an exposure of rotenone (10-6 to 10-4 M) for 24 and 48 hours. Cytotoxicity studies were carried out using standard end points including, (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) release and neutral red uptake (NRU). Cells were found to be vulnerable to rotenone in dose-dependent manner. In general, 10-4 and 10-5 M concentrations were found to be cytotoxic, whereas 10-6 M and lower concentrations used have shown nonsignificant effect on cell viability. Further, studies were extended to study the rotenone-induced alterations in cellular glutathione (GSH) level and dopamine DA-D2 receptor expression. Significant (p < 0.001) chronological depletion in GSH levels were recorded following rotenone exposure. Expression of dopamine DA-D2 receptor was also found to be effected significantly (p < 0.001) at 24 hours of rotenone exposure (10-4 and 10-5). However, no further depletion in the expression of dopamine DA-D2 receptor could be recorded with extended exposure period, that is, 48 hours. Rotenone at 10-6 M and lower concentrations was found to be ineffective in PC12 cells. Data suggest the vulnerability of PC12 cells against experimental exposure of rotenone, which possibly routed through dopamine DA-D2 receptor and oxidative stress machinery.
ISSN:0748-2337
1477-0393
DOI:10.1177/0748233710377776