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2009 | 69 | 3 |
Tytuł artykułu

Phenotype and energy dependent cholinotoxicity

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Cognitive defi cits in Alzheimer’s disease (AD) are caused by preferential loss of septal cholinergic neurons. We postulate that utilization of acetyl-CoA for ACh synthesis creates its defi cit for energy production in cholinergic neurons. Therefore, we investigated whether higher expression of the cholinergic phenotype could make these neurons more susceptible to putative AD pathogens. Chronic exposure of nondifferentiated (NC) and differentiated (DC) cholinergic septal neuroblastoma SN56 cells to amyloid-β, NO excess and Al inhibited pyruvate dehydrogenase (PDH) and other oxidative enzymes activities in, with similar potencies. However, they caused much greater decrease of acetyl-CoA content, cholinergic functions and viability in DC than in NC, respectively. On the other hand, both in NC and DC, Zn caused acute inhibition of PDH, aconitase and NADP isocitrate dehydrogenase, with similar Ki values of about 0.058, 0.010 and 0.005 mM, respectively. Unexpectedly, Zn-Ki for ketoglutarate dehydrogenase (KDH) in DC was 0.0005 mM, whereas in NC 0.0040 mM, respectively. Signifi - cant correlations were found between acetyl-CoA in mitochondria and mortality as well as between cytoplasmic acetyl-CoA and expression of the cholinergic phenotype in SN56 cells. We postulate that these two partially independent pools of acetyl-CoA affect survival and transmitter functions of cholinergic neurons, respectively. Supported by MNiSW grants 2P05A 11030, NN401139933 and AMG project St-57.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
69
Numer
3
Opis fizyczny
p.285
Twórcy
autor
  • Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland
  • Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland
autor
  • Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland
autor
  • Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland
autor
  • Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland
  • Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-0c164d0d-2b6f-4082-bef6-65f3c99e99fa
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