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Overexpression of PrP c triggers caspase 3 activation: potentiation by proteasome inhibitors and blockade by anti‐PrP antibodies
Author(s) -
Paitel E.,
Alves da Costa C.,
Vilette D.,
Grassi J.,
Checler F.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01234.x
Subject(s) - staurosporine , transfection , intracellular , microbiology and biotechnology , apoptosis , caspase , hek 293 cells , proteasome , internalization , programmed cell death , biology , cell culture , caspase 3 , caspase 8 , dna fragmentation , chemistry , cell , signal transduction , protein kinase c , biochemistry , genetics
We examined the influence of cellular prion protein (PrP c ) in the control of cell death in stably transfected HEK293 cell line and in the PrP c ‐inducible Rov9 cells. PrP c expression in stably transfected HEK293 human cells did not modify basal apoptotic tonus but drastically potentiated staurosporine‐stimulated cellular toxicity and DNA fragmentation as well as caspase 3‐like activity and immunoreactivity. An identical staurosporine‐induced caspase 3 activation was observed after doxycycline in the PrP c ‐inducible Rov9 cell line. Interestingly, proteasome inhibitors increase PrP c ‐like immunoreactivity and unmasked a basal caspase 3 activation. Conversely, we show that anti‐PrP c antibodies sequestrate PrP c at the cell surface and drastically lower PrP c ‐dependent caspase activation. We suggest that intracellular PrP c could sensitize human cells to pro‐apoptotic phenotype and that blockade of PrP c internalization could be a track to prevent intracellular toxicity associated with PrP c overexpression.