Lipocalin-2 inhibition alleviates neural injury by microglia ferroptosis suppression after experimental intracerebral hemorrhage in mice via enhancing ferritin light chain expression.
Biochim Biophys Acta Mol Basis Dis
; 1870(7): 167435, 2024 10.
Article
de En
| MEDLINE
| ID: mdl-39067535
ABSTRACT
INTRODUCTION:
Microglia play pivotal roles in post-intracerebral hemorrhage (ICH) neural injury. Iron metabolism, which is dysregulated after ICH, participates in microglial dysfunction. Previous studies have shown that iron metabolism-related lipocalin-2 (LCN2) is involved in regulating microglial function following ICH. In this study, we investigated the role of LCN2 in microglial function following ICH.METHODS:
The BV2 (microglia) cell line, transfected with LCN2 for overexpression/interference, received a blood infusion from C57BL/6 mice in vitro. For the in vivo study of LCN2 function, an LCN2 knockout was conducted in mice. Liproxstatin-1 and RSL3 were used to manipulate ferroptosis and to study the effects of LCN2 on microglia after ICH. A BV2 (microglia) cell line, transfected with ferritin light chain (FTL) for overexpression/interference, was co-cultured with primary cultured neurons for a study on the mechanism of LCN2. Behavioral tests were conducted pre-ICH and on days 3, 7, and 28 post-ICH, and the brains and cultured cells were collected for protein, histological, and morphological studies.RESULTS:
Brain LCN2 expression was upregulated in microglia, astrocytes, and neurons and played hazardous roles after ICH. In microglia, LCN2 promoted ferroptosis, which facilitated neural injury after ICH. LCN2-mediated FTL deficiency was shown to be responsible for microglial ferroptosis-induced neural injury.CONCLUSION:
Our study suggests that LCN2-enhanced microglial ferroptosis plays a detrimental role by inducing FTL deficiency after ICH. The current study reveals a novel molecular mechanism involved in the pathophysiological progression of ICH.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Hémorragie cérébrale
/
Microglie
/
Souris knockout
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Lipocaline-2
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Ferroptose
Limites:
Animals
Langue:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
/
Biochim. biophys. acta, Mol. basis dis
/
Biochimica et biophysica acta. Molecular basis of disease
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Pays-Bas