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-D(2) 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-D(2) receptor expression. Significant (p < 0.001) chronological depletion in GSH levels were recorded following rotenone exposure. Expression of dopamine DA-D(2) 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-D(2) 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-D(2) receptor and oxidative stress machinery.
Siddiqui
M A
MA
Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Kashyap
M P
MP
Khanna
V K
VK
Yadav
S
S
Al-Khedhairy
A A
AA
Musarrat
J
J
Pant
A B
AB
D000818:Animals; D005978:Glutathione / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012402:Rotenone / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D018675:Toxicity Tests
D007306:Insecticides; D017448:Receptors, Dopamine D2; D013778:Tetrazolium Salts; D013844:Thiazoles; D012402:Rotenone; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D005978:Glutathione