NR AWLQ
AU Pastore,M.; Solasso,J.; Crozet,C.A.; Lehmann,S.
TI Copper and hydrogen peroxide act in synergy for prion decontamination
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions SA-13
PT Konferenz-Poster
AB
Over the past five years, a growing interest has emerged in the role of metal ions in transmissible spongiform encephalophathies (TSEs). The amino terminus of PrPc contains indeed a series of octapeptide repeats, which are among the most conserved regions of mammalian PrPs, and have been implicated in the binding of divalent metal ions, particularly copper [1]. Whether this binding is of structural or functional significance is still elusive. Copper is an essential redox transition element able to induce ion-mediated damage to proteins. This process has been known since 1894 as the Fenton reaction and consists of reduction of Cu2+ by an electron donor and generation of the hydroxyl radical through the reduction of hydrogen peroxide (H2O2) by the reduced metal. We demonstrated previously that PrPc undergoes a site-specific cleavage of the octapeptide repeat region on exposure to Cu2+ and H2O2 [2]. In view of this, we investigated the effect on PrPsc and demonstrated the interest for a novel copper - hydrogen peroxide formulation for prion decontamination. Here, we show that a formulation of copper metal ions in combination with hydrogen peroxide has a dramatic reduction effect on PrPsc present in prion infected brain homogenates including samples from human CJDs. Animal assays confirmed the reduction effect on prion infectivity which put forward the major interest of this novel copper - hydrogen peroxide formulation for prion decontamination [3].
[1] Lehmann S. Metal ions and prion diseases. Curr Opin Chem Biol 2002; 6:187-92. [2] McMahon HE, Mange A, Nishida N, Creminon C, Casanova D and Lehmann S. Cleavage of the amino-terminus of the prion protein by reactive oxygen species. J. Biol. Chem. 2001; 276:2286-91. [3] Solassol J. Pastore M., Crozet C., Perrier V. and Lehmann S. A novel copper - hydrogen peroxide formulation for prion decontamination. JID. 2006. In press.
AD M. Pastore, C. Crozet: Institute of Human Genetics, CNRS UPR1142, Montpellier, France; J. Solassol: Cell biology Laboratory, A. de Villeneuve Hospital, Montpellier, France; S. Lehmann: Institute of Human Genetics, CNRS UPR1142, Montpellier, France, and Biochemistry Laboratory, St. Eloi Hospital, Montpellier, France. Email-address: Manuela.Pastore@igh.cnrs.fr
SP englisch
PO Italien
EA Poster, Übersicht, Ausschnitt 1a, Ausschnitt 1b, Ausschnitt 2