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, Ordoño, Jesús, DeGregorio-Rocasolano, Núria, Melià-Sorolla, Marc, Odendaal, Karla, Martí-Sistac, Octavi and Gasull, Teresa 2023. 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. Antioxidants 12 (11) , 1945. 10.3390/antiox12111945

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Abstract

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 safe and also beneficial when given after the induction of intracerebral hemorrhage (ICH) in mice, and investigated 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 h after 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 transferrin levels in the ipsilateral brain hemisphere. Although the administration of human ATf (hATf) to ICH mice did not alter the hemorrhage volume or levels of the classical ferroptosis GPX4/system xc- pathways, 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	MDPI
ISSN:	2076-3921
Date of First Compliant Deposit:	27 November 2023
Date of Acceptance:	9 October 2023
Last Modified:	29 Nov 2023 10:31
URI:	https://orca.cardiff.ac.uk/id/eprint/164394

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