Nucleofection of Rat Pheochromocytoma PC-12 Cells with Human Mutated Beta-Amyloid Precursor Protein Gene (APP-sw)‎ Leads to Reduced Viability, Autophagy-Like Process, and Increased Expression and Secretion of Beta Amyloid

Abstract EN

Pheochromocytoma PC-12 cells are immune to physiological stimuli directed to evoke programmed cell death.

Besides, metabolic inhibitors are incapable of sensitizing PC-12 cells to extrinsic or intrinsic apoptosis unless they are used in toxic concentrations.

Surprisingly, these cells become receptive to cell deletion after human APP-sw gene expression.

We observed reduced cell viability in GFP vector + APP-sw-nucleofected cells (drop by 36%) but not in GFP vector − or GFP vector + APP-wt-nucleofected cells.

Lower viability was accompanied by higher expression of Aβ 1-16 and elevated secretion of Aβ 1-40 (in average 53.58 pg/mL).

At the ultrastructural level autophagy-like process was demonstrated to occur in APP-sw-nucleofected cells with numerous autophagosomes and multivesicular bodies but without autolysosomes.

Human APP-sw gene is harmful to PC-12 cells and cells are additionally driven to incomplete autophagy-like process.

When stimulated by TRAIL or nystatin, CLU protein expression accompanies early phase of autophagy.