Targeting Pro-Oxidant Iron with Exogenously Administered Apotransferrin Provides Benefits Associated with Changes in Crucial Cellular Iron Gate Protein TfR in a Model of Intracerebral Hemorrhagic Stroke in Mice
García Serran, Alexia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ordoño, Jesus (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
De Gregorio-Rocasolano, Nuria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Melià Sorolla, Marc (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Odendaal, Karla (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martí-Sistac, Octavi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Gasull Dalmau, Teresa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	We have previously demonstrated that the post-stroke administration of iron-free transferrin (apotransferrin, ATf) is beneficial in different models of ischemic stroke (IS) through the inhibition of the neuronal uptake of pro-oxidant iron. In the present study, we asked whether ATf is safeand also beneficial when given after the induction of intracerebral hemorrhage (ICH) in mice, andinvestigated the underlying mechanisms. We first compared the main iron actors in the brain of IS-or collagenase-induced ICH mice and then obtained insight into these iron-related proteins in ICH 72 hafter the administration of ATf. The infarct size of the IS mice was double that of hemorrhage in ICH mice, but both groups showed similar body weight loss, edema, and increased ferritin and transferrinlevels in the ipsilateral brain hemisphere. Although the administration of human ATf (hATf) to ICHmice did not alter the hemorrhage volume or levels of the classical ferroptosis GPX4/system xcpathways, hATf induced better neurobehavioral performance, decreased 4-hydroxynonenal levels and those of the second-generation ferroptosis marker transferrin receptor (TfR), and restored the mRNA levels of the recently recognized cytosolic iron chaperone poly(RC) binding protein 2. In addition, hATf treatment lowered the ICH-induced increase in both endogenous mouse transferrin mRNA levels and the activation of caspase-2. In conclusion, hATf treatment provides neurobehavioral benefits post-ICH associated with the modulation of iron/oxidative players.
Ajuts:	Instituto de Salud Carlos III PI18/01813 Instituto de Salud Carlos III PI21/01925
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Apotransferrin ; Intracerebral hemorrhage ; Ischemic stroke ; Iron ; Mouse ; Oxidation
Publicat a:	Antioxidants, Vol. 12 Núm. 11 (October 2023) , ISSN 2076-3921

DOI: 10.3390/antiox12111945
PMID: 38001798

18 p, 4.0 MB

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