Cellular prion protein regulates intracellular hydrogen peroxide level and prevents copper-induced apoptosis.
The function of cellular prion protein (PrPC), which is a copper binding protein, remains unclear. To elucidate the mechanisms in which PrPC is involved in neuroprotection, we compared death signals in prion protein gene-deficient (Prnp-/-) primary cerebellar granular neurons (CGNs) to those with wild-type (WT) CGNs. When copper was exposed to these CGNs, ZrchI, and Rikn Prnp-/- CGNs were more sensitized and underwent apoptotic cell death more readily than WT CGNs. Furthermore, the level of intracellular hydrogen peroxide (H2O2) in WT CGNs increased by copper toxicity, whereas those in ZrchI and Rikn Prnp-/- CGNs did not. These results suggest that PrPC modulates the intracellular H2O2 level as a copper-binding protein to protect CGNs from apoptotic cell death possibly due to inhibiting a Fenton reaction.
Nishimura
Takuya
T
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Sakudo
Akikazu
A
Nakamura
Izuru
I
Lee
Deug-Chan
DC
Taniuchi
Yojiro
Y
Saeki
Keiichi
K
Matsumoto
Yoshitsugu
Y
Ogawa
Masaharu
M
Sakaguchi
Suehiro
S
Itohara
Shigeyoshi
S
Onodera
Takashi
T
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002531:Cerebellum / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D013997:Time Factors
D011328:Prions; D003300:Copper; D006861:Hydrogen Peroxide