Knockout of AKAP150 improves impaired BK channel-mediated vascular dysfunction through the Akt/GSK3ß signalling pathway in diabetes mellitus.
J Cell Mol Med
; 24(8): 4716-4725, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-32163656
ABSTRACT
Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel-mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150-/- ) and wild-type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150-/- diabetic mice. Impaired Akt/GSK3ß signalling contributed to decreased BK-ß1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK-ß1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK-ß1 expression, and treatment with AKAP150 siRNA suppressed GSK3ß expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel-mediated vascular dysfunction through the Akt/GSK3ß signalling pathway in diabetes mellitus.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complicações do Diabetes
/
Diabetes Mellitus Experimental
/
Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta
/
Proteínas de Ancoragem à Quinase A
/
Glicogênio Sintase Quinase 3 beta
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China