Journal of Clinical & Experimental Pathology
Open Access

Abstract

Cholinergic neurons produce acetyl-CoA, which is subsequently used as a fuel for energy production. Exclusively those neurons produce acetylcholine from acetyl-CoA. Consequently, extra utilization pathway may induce acetyl-CoA shortages and consequently impairment of brain energy metabolism. Disturbances in Ca signaling could play regulatory role in neurons susceptibility to neurodegenerative conditions. The aim of our study was to investigate whether the Voltage-Gated Calcium Channels (VGCCs) could moderate the cholinergic neurons susceptibility on neurodegeneration. Selected blockers of VGCCs (10 �?¼M nifedipine, 0.2 �?¼M Ï�?-conotoxin-MVIIC, 0.5 �?¼M Ï�?-conotoxin-GVIA) were used as a Ca depletion factors in SN56 neuroblastoma cells. Short term SN56 cells exposition on 0.15 mM Zn increased the Zn level from 0.6 to 36 nmol/mg protein. However, in the presence of 10 �?¼M nifedipine and Ï�?-conotoxins, the Zn-accumulation was decreased by about 50%. Zn caused in SN56 about 49% increase of non-viable cells fraction; whereas incubation cells with VGCCs blockers and Zn led to 25% decline in the number of trypan blue positive cells. The acetyl-CoA level in SN56 was 26.9 pmol/mg proteins. However, the SN56 cells exposition on 0.15 mM Zn decreased its level by 43%. In addition, acetyl-CoA level in VGCCs blocked SN56 was as high as in control conditions. Achieved results indicated that VGCCs regulated the Zn evoked neurotoxic effects on acetyl-CoA metabolism in SN56 cholinergic cells. Moreover, VGCCs might play particular role in neurotoxicity of Zn and show that disturbance of Ca homeostasis in this condition can be one of the factors which moderate acetyl-CoA metabolism in cholinergic neurons.

Biography

Email: marzysk@gumed.edu.pl