Zinc as early neurotoxic signal in cholinergic SN56 neuroblastoma cells

• Autorzy: Dys A. , Ronowska A. , Gul-Hinc A.S. , Klimaszewska-Lata J. , Kocbuch K. , Szutowicz A. , Bielarczyk H.
• Języki publikacji: EN

Abstrakty

EN

Preferential loss of septal cholinergic neurons is a main cause of cognitive deficits in various encephalopathies. Zinc excess is one of multiple pathologic signals contributing to mechanisms of Alzheimer’s and other neurodegenerative diseases. We suggest that zinc may be involved in early excitotoxic phase of neuronal injury. In homogenates of SN56 cholinergic neuroblastoma cells, Zn caused instant inhibition of pyruvate dehydrogenase (PDH), aconitase, isocitrate dehydrogenase (IDH) and ketoglutarate dehydrogenase (KDH) activities with Ki values equal to 0.08, 0.008, 0.005 and 0.005 mM, respectively. Short term, 30 minute exposition to Zn caused a concentration dependent increase in mortality of cAMP/retinoic acid differentiated SN56 cholinergic cells (DC) that was two times higher than that of differentiated ones (NC). Zn also decreased cytoplasmic acetyl-CoA as well as ACh content and inhibited its release. Exposition of DC and NC to increasing concentrations of Zn yielded concave up non saturable accumulation plots that reached level of 60 nmol/mg protein at 0,15 mM extracellular concentration of a cation. In these conditions no change in whole cell Ca level was observed. However the level of intramitochondrial Ca was decreased by 30%, at 100 % increase of cytoplasmic Ca. Significant, direct correlation between Zn accumulation and cytoplasmic Ca concentration (r=0.97, p=0.028) and the inverse one with mitochondrial Ca (r=- 0.96, p=0.028) were found, respectively. On the other hand, 24 h cell exposition to 0,15 mM Zn increased its intracellular content from 1.4 to about 6 nmol/mg protein at simultaneous 40% decrease of whole cell Ca level. Zn caused no significant changes in the density of ZnT1 and ZnT4 transporter proteins in the cells. Presented data indicate the coexistence in SN56 cell plasma membranes low density - high-affinity and high density - low affinity Zn-transporting sites. Inhibition of mitochondrial Na-Ca exchanger by accumulated Zn might cause depletion of Ca in mitochondria. In addition chronic exposition to Zn apparently induced adaptative mechanisms eliminating excess of the metal from the cells. These changes may directly inhibit intramitochondrial acetyl-CoA synthesis and its transport to cytoplasmic compartment, yielding impairment of cell viability and suppression their transmitter functions. Supported by MWiSW NN401 0299 37, St57 and W-109 MUG projects.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.152

Twórcy

autor

Dys A.

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

autor

Ronowska A.

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

autor

Gul-Hinc A.S.

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

autor

Klimaszewska-Lata J.

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

autor

Kocbuch K.

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

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