TY - JOUR
T1 - Scrapie-infected mice and PrP knockout mice share abnormal localization and activity of neuronal nitric oxide synthase
AU - Keshet, Gilmor I.
AU - Ovadia, Haim
AU - Taraboulos, Albert
AU - Gabizon, Ruth
PY - 1999
Y1 - 1999
N2 - PrP(Sc), the only identified component of the scrapie prion, is a conformational isoform of PrP(c). The physiological role of PrP(c), a glycolipid-anchored glycoprotein, is still unknown. We have shown previously that neuronal nitric oxide synthase (nNOS) activity is impaired in the brains of mice sick with experimental scrapie as well as in scrapie-infected neuroblastoma cells. In this work we investigated the cell localization of nNOS in brains of wild-type and scrapie-infected mice as well as in mice in which the PrP gene was ablated. We now report that whereas in wild-type mice, nNOS, like PrP(c), is associated with detergent-insoluble cholesterol-rich membranous microdomains (rafts), this is not the case in brains of scrapie- infected or in those of adult PrP(o/o) mice. Also, adult PrP(o/o), like scrapie-infected mice, show reduced nNOS activity. We suggest that PrP(c) may play a role in the targeting of nNOS to its proper subcellular localization. The similarities of nNOS properties in PrP(o/o) as compared with scrapie- infected mice suggest that at least this role of PrP(c) may be impaired in scrapie-infected brains.
AB - PrP(Sc), the only identified component of the scrapie prion, is a conformational isoform of PrP(c). The physiological role of PrP(c), a glycolipid-anchored glycoprotein, is still unknown. We have shown previously that neuronal nitric oxide synthase (nNOS) activity is impaired in the brains of mice sick with experimental scrapie as well as in scrapie-infected neuroblastoma cells. In this work we investigated the cell localization of nNOS in brains of wild-type and scrapie-infected mice as well as in mice in which the PrP gene was ablated. We now report that whereas in wild-type mice, nNOS, like PrP(c), is associated with detergent-insoluble cholesterol-rich membranous microdomains (rafts), this is not the case in brains of scrapie- infected or in those of adult PrP(o/o) mice. Also, adult PrP(o/o), like scrapie-infected mice, show reduced nNOS activity. We suggest that PrP(c) may play a role in the targeting of nNOS to its proper subcellular localization. The similarities of nNOS properties in PrP(o/o) as compared with scrapie- infected mice suggest that at least this role of PrP(c) may be impaired in scrapie-infected brains.
KW - Gene ablation
KW - Nitric oxide synthase
KW - Prion
KW - PrP protein
KW - Scrapie
UR - http://www.scopus.com/inward/record.url?scp=0033012137&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1999.0721224.x
DO - 10.1046/j.1471-4159.1999.0721224.x
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C2 - 10037495
AN - SCOPUS:0033012137
SN - 0022-3042
VL - 72
SP - 1224
EP - 1231
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 3
ER -