Hemopexin-dependent heme uptake via endocytosis regulates the Bach1 transcription repressor and heme oxygenase gene activation.
Biochim Biophys Acta
; 1840(7): 2351-60, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24613679
ABSTRACT
BACKGROUND:
Intracellular heme plays versatile roles in a variety of physiological processes including mitochondrial respiration. Heme also induces the expression of genes such as heme oxygenase-1 (HO-1) by inactivating the transcription repressor Bach1 through direct binding. However, the source of heme for the regulation of the Bach1-HO-1 axis has been unclear. Considering that extracellular heme exists as a complex with hemopexin (Hx) in serum under the physiological conditions, heme-Hx complex may deliver heme for the gene regulation.METHODS:
Using a mammalian expression system, high secretory recombinant Hx (rHx) was developed. We examined the effects of rHx-bound heme on HO-1 expression and Bach1 in Hepa-1c1c7 liver cells and THP-1 macrophage cells. We investigated the uptake pathway of rHx-bound heme by treating cells with chlorpromazine (CPZ).RESULTS:
rHx-bound heme induced the expression of HO-1 and decreased the level of Bach1 protein. CPZ inhibited the induction of the HO-1 expression by rHx-bound heme.CONCLUSION:
rHx-bound heme was internalized into the cells via endocytosis, resulting in HO-1 expression and inactivation of Bach1. GENERALSIGNIFICANCE:
The Bach1-dependent repression of the HO-1 expression is under the control of the Hx-dependent uptake of extracellular heme. Heme may regulate Bach1 as an extracellular signaling molecule.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hemopexina
/
Heme Oxigenase-1
/
Fatores de Transcrição de Zíper de Leucina Básica
/
Proteínas de Grupos de Complementação da Anemia de Fanconi
/
Heme
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Japão