Impairment of cholinergic septal SN56 cells by thiamin deficiency

• Autorzy: Bizon-Zygmanska D. , Bielarczyk H. , Jankowska-Kulawy A. , Szutowicz A.
• Języki publikacji: EN

Abstrakty

EN

Cholinergic dementias are accompanied by inhibition of pyruvate and ketoglutarate dehydrogenase (PDH, KDH) in affected brains. Therefore, we investigated how amprolium-evoked thiamine pyrophosphate defi cits impair acetyl-CoA metabolism as well as function and viability of cholinergic neurons. Two day exposure of differentiated (DC) or nondifferentiated (NC) SN56 cholinergic cells cultured in Minimal Eagles Medium to amprolium caused concentration-dependent inhibition of cell MTT reducing capacity and increased their mortality, that at 5 mM inhibitor concentration reached values 30 and 15% or 43 and 10%, respectively. However, neither PDH nor KDH activities nor cell growth were signifi cantly, inhibited by their culture with amprolium. On the other hand, amprolium decreased acetyl-CoA levels in DC and NC by 39 and 46%, respectively. The inhibitor altered choline acetyltransferase activity neither in NC nor in DC. Acetylcholine content in DC and was suppressed by amprolium for over 40%. On the contrary, in NC it had no effect on the transmitter level. These fi ndings indicate that increased ACh synthesis in DC made them more vulnerable to acetyl-CoA shortages caused by amprolium-evoked inhibition of thiamine uptake. Low rate of ACh synthesis in NC, allowed them to save more acetyl-CoA to support energy metabolism and thereby facilitated their survival under pathologic conditions. Supported by MNiSW projects PO5A 11030, NN401 2333 33 and AMG fund W-144.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.316-317

Twórcy

autor

Bizon-Zygmanska D.

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

autor

Bielarczyk H.

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

autor

Jankowska-Kulawy A.

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

autor

Szutowicz A.

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