Phenotype and energy dependent cholinotoxicity

• Autorzy: Szutowicz A. , Bielarczyk H. , Ronowska A. , Dys A. , Gul-Hinc S. , Jankowska-Kulawy A.
• 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.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.285

Twórcy

autor

Szutowicz A.

• Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Bielarczyk H.

• Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Ronowska A.

• Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Dys A.

• Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Gul-Hinc S.

• Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Jankowska-Kulawy A.

• Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland