Increased p53 levels without caspase-3 activity and change of cell viability in 6-hydroxydopamine-treated CV1-P cells.
The effect of 6-hydroxydopamine (6-OHDA) on the level of p53 protein, the activity of caspase-3 and the nuclear morphology-based assessment of cell viability were compared in the nonneuronal CV1-P fibroblast and neuronal SH-SY5Y neuroblastoma cells. The level of p53 protein was increased in the low-dose range (<100 micromol/L) in both cell types, particularly in fibroblasts. In the neuroblastoma cells, a moderate p53 increase paralleled the elevated caspase-3 activity and apoptotic cell behavior. Interestingly, in the fibroblasts at the low 6-OHDA concentrations, p53 remained high during the whole experiment, and there was neither significant caspase-3 activity nor cell death. In the high-dose range (>100 micromol/L), the increase of p53 was reduced and the cell death was predominantly necrotic as judged from the nuclear morphology in both fibroblasts and neuroblastoma cells. Also, the caspase-3 activity was reduced in SH-SY5Y cells. In contrast to some earlier reports, we have shown that the actual 6-OHDA sensitivity of nonneuronal cells may be equal or even higher than that in neuronal cells if the enhancement of p53 levels is used as a criterion for the response. However, the 6-OHDA toxicity was clearly higher in the neuronal than in fibroblast cells.
Puttonen
K A
KA
Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland. katja.puttonen@uku.fi
Manáková
S
S
Raasmaja
A
A
Männistö
P T
PT
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D013565:Sympatholytics / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D013565:Sympatholytics; D016159:Tumor Suppressor Protein p53; D016627:Oxidopamine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases