Acute cytotoxicity of zinc on SN56 cholinergic cells

• Autorzy: Dys A. , Ronowska A. , Jankowska-Kulawy A. , Szutowicz A. , Bielarczyk H.
• Języki publikacji: EN

Abstrakty

EN

Zinc is a trace element essential for living organisms. However, its excess in the aging human brain is claimed to contribute to patomechanisms Alzheimerís disease. The aim of this work was to fi nd out whether acute effects of Zn on neurons may be caused by alterations in their acetyl-CoA metabolism. Zn quickly accumulated in cholinergic SN56 cells in concentration-dependent fashion. In cell homogenates Zn caused, inhibition of pyruvate dehydrogenase (PDH), aconitase, isocitrate dehydrogenase and ketoglutarate dehydrogenase (KDH) activities, with Ki values equal to 0.058, 0.010, 0.005 and 0.0015 mM, respectively. For choline acetyltransferase [IC 0.5] for Zn was above 0.3 mM. No inhibition of succinate dehydrogenase activity was found. It also decreased cytoplasmic acetyl-CoA and ACh levels ([IC 0.5] 0.15 mM), and inhibited ACh release ([IC 0.5] 0.10 mM). Lipoamide (LA) or EDTA, added before or simultaneously with Zn prevented these inhibitions. When LA or EDTA were added 10 min after Zn, they did not reverse aconitase inhibition, partially restored KDH activity and totally reversed inhibition of PDH. Activities of PDH and KDH but not aconitase suppressed by 24 hour cell culture with Zn, were also restored by post culture additions of LA and EDTA to harvested cell homogenates. It indicates that, Zn could exert its acute effects on cholinergic cells through inhibitory-binding to crucial enzymes of energy metabolism, yielding acute depletion of cytoplasmic acetyl-CoA and suppression of cholinergic transmitter functions. Supported by MNiSW grants NN401 2333 33 and P05A 110 30

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.96

Twórcy

autor

Dys A.

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

autor

Ronowska A.

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

autor

Jankowska-Kulawy A.

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

autor

Szutowicz A.

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

autor

Bielarczyk H.

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