Analyse der Proteinexpression zur Untersuchung der physiologischen Funktion des zellulären Prionproteins (PrPc)

Abstract

The definite physiological role of the cellular prion protein (PrPc) remains still unclear. On the one hand there is ample in vitro and in vivo evidence suggesting a neuroprotective role for PrPc, on the other hand, several studies demonstrated detrimental or proapoptotic effects of PrPc overexpression. In this study proteome expression changes following stable PrPc overexpression in human neuronal SH-SY5Y cells are reported. In total 18 proteins that are involved in diverse biological processes were identified as differentially regulated. The majority of these proteins is involved in cell signaling, cytoskeletal organization and protein folding. Annexin V exhibited a several fold up-regulation by PrPc overexpression. This protein plays an important role in maintenance of calcium homeostasis which when disturbed can activate a p53- dependent cell death. Although changes in p53 expression between PrPc overexpressing SH-SY5Y and control cells could not be detected in this study, deregulation of several proteins including annexin V and transgelin 2 indicates disrupted cellular equilibrium. Both proteins showed a similar trend in regulation by PrPc as it was previously documented in the brains of sporadic Creutzfeldt-Jakob disease and Alzheimer disease patients, respectively. We conclude that stable PrPc overexpression in SH-SY5Y cells is sufficient to perturb cellular balance but insufficient to affect p53 expression.