Phenotype dependent differential effects of interleukin-1beta and amyloid-beta on viability and cholinergic phenotype of T17 neuroblastoma cells.
Amyloid-beta accumulation in brains of Alzheimer's disease (AD) victims is accompanied by glial inflammatory reactions and preferential loss of cholinergic neurons. Therefore, the aim of this study was to find out whether proinflamatory cytokine interleukin 1beta (IL1beta) modifies effects of amyloid-beta (Abeta) on viability and cholinergic phenotype of septum derived T17 cholinergic neuroblastoma cells. In nondifferentiated T17 cells (NC) Abeta(25-35) (1 microg/ml) caused no changes in choline acetyltransferase (ChAT) activity, acetylcholine (ACh) release, subcellular distribution of acetyl-CoA, but doubled content of trypan blue positive cells. IL1beta (10 ng/ml) increased ACh release (125%) but did not change other parameters of NC. In the presence of Abeta IL1beta also increased ChAT activity (47%), ACh release (100%) but had no effect on acetyl-CoA distribution and cell viability. Differentiation with retinoic acid and dibutyryl cyclic AMP caused over two-fold increase of ChAT activity and ACh content, four-fold increase of ACh release and about 50% decrease of acetyl-CoA level in the mitochondria. In differentiated cells (DC), Abeta decreased ChAT activity (31%), ACh release (47%) and content of acetyl-CoA (80%) in cell cytoplasmic compartment, whereas IL1beta elevated ChAT activity (54%) and ACh release (32%). IL1beta totally reversed Abeta-evoked inhibition of ChAT activity and ACh release and restored control level of cytoplasmic acetyl-CoA but increased fraction of nonviable cells to 25%. Thus, IL1beta could compensate Abeta-evoked cholinergic deficits through the restoration of adequate expression of ChAT and provision of acetyl-CoA to cytoplasmic compartment in cholinergic neurons that survive under such pathologic conditions. These data indicate that IL1beta possess independent cholinotrophic and cholinotoxic activities that may modify Abeta effects on cholinergic neurons.
Bielarczyk
Hanna
H
Department of Laboratory Medicine, Medical University of Gdańsk, Debinki 7 str., 80-211 Gdańsk, Poland.
Jankowska-Kulawy
Agnieszka
A
Gul
Sylwia
S
Pawełczyk
Tadeusz
T
Szutowicz
Andrzej
A
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D007375:Interleukin-1 / Q000494:pharmacology*; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology; D010641:Phenotype; D051381:Rats; D014343:Trypan Blue
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D007375:Interleukin-1; D000105:Acetyl Coenzyme A; D014343:Trypan Blue; D000109:Acetylcholine