Serum withdrawal-induced apoptosis in ZrchI prion protein (PrP) gene-deficient neuronal cell line is suppressed by PrP, independent of Doppel.
Previous studies have shown that cellular prion protein (PrP(C)) plays anti-apoptotic and antioxidative role against cell death induced by serum-deprivation (SDP) in an immortalized prion protein gene-deficient neuronal cell line derived from Rikn prion protein (PrP) gene-deficient (Prnp(-/-)) mice, which ectopically produce excess Doppel (Dpl) (PrP-like glycoprotein). To investigate whether PrP(C) inhibits apoptotic neuronal cell death without Dpl, an immortalized cell line was established from the brain of ZrchI Prnp(-/-) mice, which do not show ectopic expression of Dpl. The results using a ZrchI neuronal Prnp(-/-) cell line (NpL2) showed that PrP(C) potently inhibited SDP-induced apoptotic cell death. Furthermore, PrP(C) expression enhanced the superoxide dismutase (SOD) activity in NpL2 cells. These results indicate that Dpl production did not affect anti-apoptotic and anti-oxidative functions of PrP, suggesting that PrP(C) may be directly correlated with protection against oxidative stress.
Nishimura
Takuya
T
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Sakudo
Akikazu
A
Hashiyama
Yoriko
Y
Yachi
Akiko
A
Saeki
Keiichi
K
Matsumoto
Yoshitsugu
Y
Ogawa
Masaharu
M
Sakaguchi
Suehiro
S
Itohara
Shigeyoshi
S
Onodera
Takashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D058851:GPI-Linked Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions / Q000378:metabolism* / Q000494:pharmacology; D011498:Protein Precursors / Q000172:deficiency* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D058851:GPI-Linked Proteins; D000072002:Prion Proteins; D011328:Prions; C122036:Prnd protein, mouse; C512657:Prnp protein, mouse; D011498:Protein Precursors