PrP cooperates with STI1 to regulate SOD activity in PrP-deficient neuronal cell line.
Cellular prion protein (PrP(C)) plays anti-apoptotic and anti-oxidative roles in apoptosis induced by serum deprivation in an immortalized prion protein gene (Prnp)-deficient neuronal cell line. The octapeptide repeat region (OR) and N-terminal half of the hydrophobic region (HR) of PrP(C) are indispensable for PrP(C) activity, but the mechanisms remain unclear. In the present study, elucidation of the mechanisms by which PrP(C) elicits the anti-oxidative activities was facilitated by evidence of stress-inducible protein 1 (STI1) mediating PrP(C)-dependent superoxide dismutase (SOD) activation. Immunoprecipitation revealed that PrP(C) was associated with STI1. The inhibitory peptides against PrP(C)-STI1 binding [STI1 pep.1 and PrP(113-132)] indicated toxic activity in PrP(C)-expressing cells by inhibiting SOD activity but not in Prnp(-/-) cells. Furthermore, OR and N-terminal half of the HR were required for the inhibitory effect of PrP(113-132) but not STI1 pep.1. These data are consistent with results established with a model where OR and N-terminal half of the HR mediate the action of STI1 upon cell survival and upregulation of SOD activity.
Sakudo
Akikazu
A
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Lee
Deug-chan
DC
Li
Shuming
S
Nakamura
Toyoo
T
Matsumoto
Yoshitsugu
Y
Saeki
Keiichi
K
Itohara
Shigeyoshi
S
Ikuta
Kazuyoshi
K
Onodera
Takashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D018621:PrPC Proteins / Q000172:deficiency*; D011328:Prions / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; C489791:Stip1 protein, mouse; C498167:prion protein (113-132); D013482:Superoxide Dismutase