Previously, we have shown a significant increase in the expression of carbonic anhydrase VIII (CA8) in SK-N-SH-MJD78 cells, which are human neuroblastoma cells overexpressing mutant ataxin-3 with 78 glutamine repeats.
Hence, in this study we analysed the influence of these two proteins (α-Syn and wild-type or mutant Atx3) on modified redox signaling, a pathological process potentially linked to both diseases, and also the impact of exposure to iron and rotenone in SH-SY5Y neuroblastoma cells.
Compared with the cells containing normal ataxin-3, protein expression of CA8 and CA11 is significantly increased in human neuroblastoma cells harboring mutant ataxin-3.
In this study, we utilized neuroblastoma SK-N-SH cells stably transfected with full-length expanded ataxin-3 to further investigate the mechanism(s) resulting in the decreased expression of Hsp27.
We analyzed ataxin-3 proteolysis in neuroblastoma cells and in vitro and show that calcium-dependent calpain proteases generate aggregation-competent ataxin-3 fragments.
Consistently, proteolytic cleavage of full-length, pathogenic AT3 initiates the formation of sodium dodecylsulfate-resistant aggregates in neuroblastoma cells.