NR AOMX
AU Sakudo,A.; Lee,D.C.; Saeki,K.; Nakamura,Y.; Inoue,K.; Matsumoto,Y.; Itohara,S.; Onodera,T.
TI Impairment of superoxide dismutase activation by N-terminally truncated prion protein (PrP) in PrP-deficient neuronal cell line
QU Biochemical and Biophysical Research Communications 2003 Aug 29; 308(3): 660-7
PT journal article
AB Previous studies have reported a neuroprotective role for cellular prion protein (PrPc) against apoptosis induced by serum deprivation in an immortalized prion protein gene (Prnp)-deficient neuronal cell line, but the mechanisms remain unclear. In this study, to investigate the mechanisms by which PrPc prevents apoptosis, the authors compared apoptosis of Prnp(-/-) cells with that of Prnp(-/-) cells expressing the wild-type PrPc or PrPc lacking N-terminal octapeptide repeat region under serum-free conditions. Re-introduction of Prnp rescued cells from apoptosis, upregulated superoxide dismutase (SOD) activity, enhanced superoxide anion elimination, and inhibited caspase-3/9 activation. On the other hand, N-terminally truncated PrPc enhanced apoptosis accompanied by potentiation of superoxide production and caspase-3/9 activation due to inhibition of SOD. These results suggest that PrPc protects Prnp(-/-) cells from apoptosis via superoxide- and caspase-3/9-dependent pathways by upregulating SOD activity. Furthermore, the octapeptide repeat region of PrPc plays an essential role in regulating apoptosis and SOD activity.
MH Amyloid/genetics; Animal; *Apoptosis; Caspases/metabolism; Cell Line; Comparative Study; Culture Media, Serum-Free; Enzyme Activation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons/cytology/enzymology/*metabolism; PrPc Proteins/*chemistry/*physiology; Protein Precursors/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Repetitive Sequences, Amino Acid; Sequence Deletion; Superoxide Dismutase/*metabolism; Superoxides/metabolism; Support, Non-U.S. Gov't
AD Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Japan.
SP englisch
PO USA