NR ARIU
AU Nishimura,T.; Sakudo,A.; Nakamura,I.; Lee,D.C.; Taniuchi,Y.; Saeki,K.; Matsumoto,Y.; Ogawa,M.; Sakaguchi,S.; Itohara,S.; Onodera,T.
TI Cellular prion protein regulates intracellular hydrogen peroxide level and prevents copper-induced apoptosis
QU Biochemical and Biophysical Research Communications 2004 Oct 8; 323(1): 218-22
PT journal article
AB 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.
MH Animals; *Apoptosis; Cell Nucleus/metabolism; Cell Survival; Cerebellum/metabolism; Copper/*chemistry/pharmacology; Dose-Response Relationship, Drug; Flow Cytometry; Hydrogen Peroxide/*pharmacology; Mice; Mice, Inbred C57BL; Neurons/metabolism; Prions/*chemistry/genetics; Protein Binding; Research Support, Non-U.S. Gov't; Time Factors
AD Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
SP englisch
PO USA