Cellular prion protein overexpression disturbs cellular homeostasis in SH-SY5Y neuroblastoma cells but does not alter p53 expression: a proteomic study
| Autor: | Barbara Ciesielczyk, Inga Zerr, Abdul R. Asif, Joanna Gawinecka, Walter J. Schulz-Schaeffer, Matthias Schmitz, E. Weiss, Christina Behrens, Sanja Ramljak |
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| Rok vydání: | 2009 |
| Předmět: |
Proteomics
Programmed cell death Cellular homeostasis Biology Transfection 03 medical and health sciences Mice 0302 clinical medicine Annexin Cell Line Tumor Animals Homeostasis Humans PrPC Proteins 030304 developmental biology Neurons 0303 health sciences General Neuroscience HEK 293 cells Molecular biology Cell biology Cell culture biology.protein GRB2 Signal transduction Tumor Suppressor Protein p53 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neuroscience. 169(4) |
| ISSN: | 1873-7544 |
| Popis: | The definite physiological role of the cellular prion protein (PrP(c)) remains elusive. There is ample in vitro and in vivo evidence suggesting a neuroprotective role for PrP(c). On the other hand, several in vitro and in vivo studies demonstrated detrimental effects of PrP(c) overexpression through activation of a p53 pathway. Recently, we reported that transient overexpression of PrP(c) in human embryonic kidney 293 cells elicits proteome expression changes which point to deregulation of proteins involved in energy metabolism and cellular homeostasis. Here we report proteome expression changes following stable PrP(c) overexpression in human neuronal SH-SY5Y cells. 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 following stable PrP(c) overexpression in SH-SY5Y cells. This finding has been reproduced in alternative, mouse N2a and human SK-N-LO neuroblastoma cell lines transiently overexpressing PrP(c). Annexin V plays an important role in maintenance of calcium homeostasis which when disturbed can activate a p53-dependent cell death. Although we did not detect changes in p53 expression between PrP(c) overexpressing SH-SY5Y and control cells, deregulation of several proteins including annexin V, polyglutamine tract-binding protein-1, spermine synthase and transgelin 2 indicates disrupted cellular equilibrium. We conclude that stable PrP(c) overexpression in SH-SY5Y cells is sufficient to perturb cellular balance but insufficient to affect p53 expression. |
| Databáze: | OpenAIRE |
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