Activation of apoptosis by serum deprivation in a teratocarcinoma cell line: inhibition by L-acetylcarnitine.
P19 teratoma cells differentiate to neural-like cells in the presence of retinoic acid. If they are plated in N2 synthetic, serum-free medium without being exposed to retinoic acid, they die within 48-72 h. This model has allowed the discovery of the neuron survival-promoting capacity of activin. We have studied the death process triggered by serum removal, and showed that it has the characteristics of apoptosis. In addition we have used this model to study the mechanism of action of L-acetyl-carnitine. This endogenous molecule has been successfully employed as a drug retarding Alzheimer's disease progression. Many pharmacological actions have been reported for this compound. However, so far, it has been difficult to explain the observed results with a single mechanism of action. We have demonstrated that the addition of 100 microM L-acetylcarnitine to the N2 medium, at the time of plating, enhances cell survival, retarding DNA fragmentation and nuclear condensation. We have ruled out the possibility of a role of oxidative stress in the activation of apoptosis, under our conditions. Therefore the protective action of L-acetylcarnitine does not seem to be due to a putative antioxidant activity. Our data, demonstrating a retardation by L-acetylcarnitine of apoptotic cell death, could provide a unifying hypothesis for the explanation of several described actions of this drug. In the view that some of the degenerative diseases in the nervous system could be due to the presence of abnormal stimuli, or the absence of trophic factors that trigger programmed cell death, this model of serum deprivation-induced cell death seems to be relevant for the study of neuroprotective molecules.
Galli
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Fratelli
M
M
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001769:Blood; D002470:Cell Survival; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000108:Acetylcarnitine; D005978:Glutathione