Chronic insulin treatment phosphorylates the renal Na-K-ATPase α1-subunit at serine 16/23 and reduces its activity involving PI3-kinase-dependent PKC activation.
Am J Physiol Renal Physiol
; 311(5): F958-F966, 2016 11 01.
Article
en En
| MEDLINE
| ID: mdl-27605582
The regulation of Na-K-ATPase in various tissues is under the control of a number of hormones and peptides that exert both short- and long-term control over its activity. The present study was performed to investigate the effect of chronic insulin treatment on Na-K-ATPase in renal proximal tubular cells. Incubation of opossum kidney (OK) cells, transfected with the rat Na-K-ATPase α1-subunit, with 1 nmol/l insulin for 48 h decreased Na-K-ATPase activity. Insulin decreased α1-protein content and increased α1-serine phosphorylation and α1-adaptor protein 2 (AP2) interaction. Removal of the 26 NH2-terminal (-NT) amino acid from the α1-subunit containing serine/threonine sites abolished the insulin-mediated serine phosphorylation and inhibition of Na-K-ATPase. Substitution of serine 16 and 23 with alanine showed a comparable effect on -NT. Insulin increased the activity of protein kinase C (PKC), which was blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. Both PI3K and PKC inhibitors abolished the insulin-mediated inhibition of Na-K-ATPase. Insulin increased the expression of PKC-ß1, -δ, -ξ, and-λ; however, only PKC-ξ/λ-specific inhibitors blocked insulin-induced phosphorylation and inhibition of Na-K-ATPase. Our data demonstrate that insulin activates the atypical PKC isoforms-ξ/λ via the PI3K pathway. PKC-ξ/λ-induced phosphorylation of the α1-subunit at serine 16 and 23 leads to AP2 recruitment, degradation, and a decrease in Na-K-ATPase activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
ATPasa Intercambiadora de Sodio-Potasio
/
Fosfatidilinositol 3-Quinasas
/
Hipoglucemiantes
/
Insulina
/
Riñón
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Asunto de la revista:
FISIOLOGIA
/
NEFROLOGIA
Año:
2016
Tipo del documento:
Article
Pais de publicación:
Estados Unidos