Differentiated Paju cells have increased resistance to toxic effects of potassium ionophores.
In this study we have investigated the impact of differentiation of neuronal cells on their sensitivity to microbial toxins. We used the human neural crest-derived tumor cell line Paju, which can be induced to differentiation in vitro by treatment with phorbol 12-myristate 13-acetate. Addition of the highly toxic potassium ionophores cereulide (4.5 and 9.0 ng/ml) or valinomycin (20 ng/ml), to cultures of undifferentiated Paju cells caused collapse of the mitochondrial membrane potential - measured with the fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetrabenzimidazole carbocyanine iodide (JC-1) followed by detachment of the cells and their apoptotic death. After induced differentiation of the Paju cells, their mitochondria retained the membrane potential upon exposure to the toxins and the cells displayed increased resistance to apoptosis as compared with undifferentiated cells. This effect may be caused by an elevated expression of the anti-apoptotic protein Bcl-2 and of the neuroprotective factor, stanniocalcin, in differentiated cells.
Teplova
Vera
V
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, RU-142290 Pushchino, Moscow region, Russia.
Jääskeläinen
Elina
E
Salkinoja-Salonen
Mirja
M
Saris
Nils-Erik L
NE
Serlachius
Martina
M
Li
Feng-Yen
FY
Andersson
Leif C
LC
D017209:Apoptosis; D001562:Benzimidazoles / Q000494:pharmacology; D002232:Carbocyanines / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology* / Q000633:toxicity; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D011188:Potassium / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D001562:Benzimidazoles; D002232:Carbocyanines; D047630:Depsipeptides; D005456:Fluorescent Dyes; D006023:Glycoproteins; D007476:Ionophores; D019253:Proto-Oncogene Proteins c-bcl-2; C089294:cereulide; D014634:Valinomycin; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; C051795:teleocalcin; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium