Calreticulin protects insulin against reductive stress in vitro and in MIN6 cells.
Biochimie
; 171-172: 1-11, 2020.
Article
em En
| MEDLINE
| ID: mdl-32004653
ABSTRACT
Oxidative folding of proinsulin in the endoplasmic reticulum (ER) is critical for the proper sorting and secretion of insulin from pancreatic ß-cells. Here, by using non-cell-based insulin aggregation assays and mouse insulinoma-derived MIN6 cells, we searched for a candidate molecular chaperone for (pro)insulin when its oxidative folding is compromised. We found that interaction between insulin and calreticulin (CRT), a lectin that acts as an ER-resident chaperone, was enhanced by reductive stress in MIN6 cells. Co-incubation of insulin with recombinant CRT prevented reductant-induced aggregation of insulin. Furthermore, lysosomal degradation of proinsulin, which was facilitated by dithiothreitol-induced reductive stress, depended on CRT in MIN6 cells. Together, our results suggest that CRT may be a protective molecule against (pro)insulin aggregation when oxidative folding is defective, e.g. under reductive stress conditions, in vitro and in cultured cells. Because CRT acts as a molecular chaperone for not only glycosylated proteins but also non-glycosylated polypeptides, we also propose that (pro)insulin is a novel candidate client of the chaperone function of CRT.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proinsulina
/
Chaperonas Moleculares
/
Calreticulina
/
Células Secretoras de Insulina
/
Secreção de Insulina
Limite:
Animals
Idioma:
En
Revista:
Biochimie
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão