Cellular prion protein suppressess the apoptotic cell death by mediating the intracellular H2O2 in primary culture and immortalized neuronal cells
Izuru Nakamura, Takuya Nishimura, Keiichi Saeki, Yoshitsugu Matsu- moto, and Takashi Onodera
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 Japan <e-mail> aa37121@mail.ecc.u-tokyo.ac.jp
Abstract
To know the mechanisms in which cellular isoform of prion protein (PrP^) is involved for the neuroprotection, we compared death signals in Pmp'^"
primary cultivated neurons to those in wild-type (WT) primary cultivated neurons. These results are also confirmed by immortarized neuronal cells. When copper was exposed to these neurons, the both of type-1 and type-2 Pmp"^" neurons were more sensitive and underwent apoptotic cell death more readily than WT neurons. The cell death in Pmp"^" neurons was effectively inhibited by anti-oxidants or some caspase-inhibitors as seen in wild-type neurons. In Pmp"^" neurons, copper toxicity was en- hanced more significantly by deprivation of anti-oxidants, and then in- duced more increasing apoptotic features. To know the level of the reac- tive oxygen species, the level of the intracellular hydrogen peroxide (H2O2) were measured. Intracellular H2O2 in Pmp"^" cells decreased more rapidly than that in WT cells. These data demonstrate that in Pmp'^" neu- rons, copper may be a strong mediator to convert H2O2 to more toxic free radicals in a fenton-like reaction, which induces more caspase-mediated apoptosis. These results suggest that PrP^ may moderate the intracellular H2O2 level as a copper binding protein or an anti-oxidant to protect neu- ronal cells from apoptotic death.
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