Cell density impacts the susceptibility to ferroptosis by modulating IRP1-mediated iron homeostasis.
J Neurochem
; 168(7): 1359-1373, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38382918
ABSTRACT
Ferroptosis has been implicated in several neurological disorders and may be therapeutically targeted. However, the susceptibility to ferroptosis varies in different cells, and inconsistent results have been reported even using the same cell line. Understanding the effects of key variables of in vitro studies on ferroptosis susceptibility is of critical importance to facilitate drug discoveries targeting ferroptosis. Here, we showed that increased cell seeding density leads to enhanced resistance to ferroptosis by reducing intracellular iron levels. We further identified iron-responsive protein 1 (IRP1) as the key protein affected by cell density, which affects the expression of ferroportin or transferrin receptor and results in altered iron levels. Such observations were consistent across different cell lines, indicating that cell density should be tightly controlled in studies of ferroptosis. Since cell densities vary in different brain regions, these results may also shed light on selective regional vulnerability observed in neurological disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína 1 Reguladora do Ferro
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Ferroptose
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Homeostase
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Ferro
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2024
Tipo de documento:
Article