Differentiation of PC12 cells induced by N8-acetylspermidine and by N8-acetylspermidine deacetylase inhibition.
Spermidine is one of the simple polyamines found in cells of virtually all living organisms. It undergoes a metabolic conversion to N8-acetylspermidine catalyzed by an enzyme in cell nuclei and is converted back to spermidine by a deacetylase in the cytoplasm. In this study, two different mechanisms were used to produce an elevation in the level of N8-acetylspermidine in PC12 cells: inhibition of N8-acetylspermidine deacetylase and direct addition of N8-acetylspermidine to the cell culture. The increasing intracellular concentration of N8-acetylspermidine was accompanied by signs of PC12 cell differentiation including increased content of dopamine and morphological changes (neurite outgrowths), suggesting a strong and perhaps causal relationship among these effects. This effect on differentiation appears to be specific for N8-acetylspermidine as the addition of other polyamines including spermidine and N1-acetylspermidine did not elicit these changes. Nerve growth factor (NGF) and dexamethasone, commonly used inducers of differentiation in PC12 cells, produced differentiation without measurable changes in N8-acetylspermidine levels, suggesting that different (or multiple) mechanisms may be involved in these differentiation processes.
Mudumba
Sreenivasu
S
Department of Pharmacology, School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA.
Menezes
Ana
A
Fries
David
D
Blankenship
Jim
J
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D013095:Spermidine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D011073:Polyamines; C030223:N(8)-acetylspermidine; D003907:Dexamethasone; D020932:Nerve Growth Factor; D000581:Amidohydrolases; C018738:acetylspermidine deacetylase; D013095:Spermidine; D004298:Dopamine