The essential role of the transporter ABCG2 in the pathophysiology of erythropoietic protoporphyria.
Sci Adv
; 5(9): eaaw6127, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31555729
ABSTRACT
Erythropoietic protoporphyria (EPP) is an inherited disease caused by loss-of-function mutations of ferrochelatase, an enzyme in the heme biosynthesis pathway that converts protoporphyrin IX (PPIX) into heme. PPIX accumulation in patients with EPP leads to phototoxicity and hepatotoxicity, and there is no cure. Here, we demonstrated that the PPIX efflux transporter ABCG2 (also called BCRP) determines EPP-associated phototoxicity and hepatotoxicity. We found that ABCG2 deficiency decreases PPIX distribution to the skin and therefore prevents EPP-associated phototoxicity. We also found that ABCG2 deficiency protects against EPP-associated hepatotoxicity by modulating PPIX distribution, metabolism, and excretion. In summary, our work has uncovered an essential role of ABCG2 in the pathophysiology of EPP, which suggests the potential for novel strategies in the development of therapy for EPP.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Protoporfirinas
/
Pele
/
Protoporfiria Eritropoética
/
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article