title: Acetyl-CoA metabolism in amprolium-evoked thiamine pyrophosphate deficits in cholinergic SN56 neuroblastoma cells.
abstract: Inhibition of pyruvate (PDHC) and ketoglutarate (KDHC) dehydrogenase complexes induced by thiamine pyrophosphate deficits is known cause of disturbances of cholinergic transmission in the brain, yielding clinical symptoms of cognitive, vegetative and motor deficits. However, particular alterations in distribution of key acetylcholine precursor, acetyl-CoA, in the cholinergic neuron compartment of thiamine pyrophosphate-deficient brain remain unknown. Therefore, the aim of our work was to find out how amprolium-induced thiamine pyrophosphate deficits (TD) affect distribution of acetyl-CoA in the compartment of pure cholinergic neuroblastoma SN56 cells originating from murine septum. Amprolium caused similar concentration-dependent decreases in thiamine pyrophosphate levels in nondifferentiated (NC) and differentiated (DC) cells cultured in low thiamine medium. In such conditions DC displayed significantly greater loss of viability than the NC ones, despite of lesser suppressions of PDHC activities and tetrazolium salt reduction rates in the former. On the other hand, intramitochondrial acetyl-CoA levels in DC were 73% lower than in NC, which explains their greater susceptibility to TD. Choline acetyltransferase activity and acetylcholine content in DC were two times higher than in NC. TD caused 50% decrease of cytoplasmic acetyl-CoA levels that correlated with losses of acetylcholine pool in DC but not in NC. These data indicate that particular sensitivity of DC to TD may result from relative shortage of acetyl-CoA due to its higher utilization in acetylcholine synthesis.
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Bizon-Zygmańska
authors.forename: A
authors.initials: A
authors.lastname: Jankowska-Kulawy
authors.forename: H
authors.initials: H
authors.lastname: Bielarczyk
authors.forename: T
authors.initials: T
authors.lastname: Pawełczyk
authors.forename: A
authors.initials: A
authors.lastname: Ronowska
authors.forename: M
authors.initials: M
authors.lastname: Marszałł
authors.forename: A
authors.initials: A
authors.lastname: Szutowicz
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000670:Amprolium / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D013835:Thiamine Pyrophosphate / Q000378:metabolism*
chemical_list: D000105:Acetyl Coenzyme A; D000670:Amprolium; D013835:Thiamine Pyrophosphate