The human prion octarepeat fragment prevents and reverses the inhibitory action of copper in the P2X<sub>4</sub> receptor without modifying the zinc action

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dc.contributor.authorLorca, RA
dc.contributor.authorChacón, M
dc.contributor.authorBarría, MI
dc.contributor.authorInestrosa, NC
dc.contributor.authorHuidobro-Toro, JP
dc.date.accessioned2025-01-21T01:09:29Z
dc.date.available2025-01-21T01:09:29Z
dc.date.issued2003
dc.description.abstractHuman prion protein fragments (PrP60-67 or PrP59-91) prevented and reversed the inhibition elicited by 5 mum copper on the P2X(4) receptor expressed in Xenopus laevis oocytes. A 60-s pre-application of 5 muM copper caused a 69.2 +/- 2.6% inhibition of the 10 muM adenosine triphosphate (ATP)-evoked currents, an effect that was prevented by mixing 5 muM copper with 0.01-10 muM of the PrP fragments 1-min prior to application. This interaction was selective, as PrP59-91 did not alter the facilitatory action of zinc. The EC50 of PrP60-67 and PrP59-91 for the reduction of the copper inhibition were 4.6 +/- 1 and 1.3 +/- 0.4 muM, respectively. A synthetic PrP59-91 variant in which all four His were replaced by Ala was inactive. However, the replacement of Trp in each of the four putative copper-binding domains by Ala slightly decreased its potency. Furthermore, the application of 10 muM PrP59-91 reversed the copper-evoked inhibition, restoring the ATP concentration curve to the same level as the non-inhibited state. Fragment 139-157 of betaA4 amyloid precursor protein also prevented the action of copper; its EC50 was 1.6 +/- 0.1 muM; the metal chelator penicillamine was equipotent with PrP60-67, but carnosine was significantly less potent. Our findings highlight the role of PrP in copper homeostasis and hint at its possible role as a modulator of synapses regulated by this trace metal.
dc.fuente.origenWOS
dc.identifier.doi10.1046/j.1471-4159.2003.01705.x
dc.identifier.issn0022-3042
dc.identifier.urihttps://doi.org/10.1046/j.1471-4159.2003.01705.x
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96589
dc.identifier.wosidWOS:000182259900017
dc.issue.numero3
dc.language.isoen
dc.pagina.final716
dc.pagina.inicio709
dc.revistaJournal of neurochemistry
dc.rightsacceso restringido
dc.subjectcopper homeostasis
dc.subjectcopper neuromodulation
dc.subjectprion protein fragments
dc.subjectP2X(4) ATP-gated channels
dc.subjectnucleotide receptors
dc.subjectXenopus laevis oocytes
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe human prion octarepeat fragment prevents and reverses the inhibitory action of copper in the P2X<sub>4</sub> receptor without modifying the zinc action
dc.typeartículo
dc.volumen85
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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