title: Impairment of superoxide dismutase activation by N-terminally truncated prion protein (PrP) in PrP-deficient neuronal cell line.
abstract: Previous studies have reported a neuroprotective role for cellular prion protein (PrP(C)) 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 PrP(C) prevents apoptosis, the authors compared apoptosis of Prnp(-/-) cells with that of Prnp(-/-) cells expressing the wild-type PrP(C) or PrP(C) 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 PrP(C) enhanced apoptosis accompanied by potentiation of superoxide production and caspase-3/9 activation due to inhibition of SOD. These results suggest that PrP(C) protects Prnp(-/-) cells from apoptosis via superoxide- and caspase-3/9-dependent pathways by upregulating SOD activity. Furthermore, the octapeptide repeat region of PrP(C) plays an essential role in regulating apoptosis and SOD activity.
authors.affiliation: Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Japan.
authors.forename: Akikazu
authors.initials: A
authors.lastname: Sakudo
authors.forename: Deug-chan
authors.initials: DC
authors.lastname: Lee
authors.forename: Keiichi
authors.initials: K
authors.lastname: Saeki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
mesh_terms: D000682:Amyloid / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D018621:PrPC Proteins / Q000737:chemistry* / Q000502:physiology*; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000682:Amyloid; D016895:Culture Media, Serum-Free; D018621:PrPC Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D013481:Superoxides; D013482:Superoxide Dismutase; D020169:Caspases