Der Einfluss von advanced glycation end-products auf die podozytäre Expression des nuklearen Inhibitors der Proteinphosphatase 1

Liebisch, Marita GND

Advanced glycation end-products (AGEs) are generated in the Maillard reaction by non-enzymatic glycation of proteins by reducing sugars. They exhibit pathophysiological effects. Of particular importance is the receptor for AGEs RAGE. Diabetes mellitus is associated with hyperglycemia that induces the formation and accumulation of AGEs. The increased AGE exposition can damage renal cells such as podocytes. Podocytes are glomerular cells that play an important role in the organization of the glomerular ultrafiltration barrier. Differential Display analysis showed that incubation of murine, conditionally differentiated podocytes with glycated albumin (AGE-BSA) affects the expression of different genes compared with the non-glycated control BSA, among them NIPP1, the nuclear inhibitor of protein phosphatase 1 (PP1). Real-time PCR, Western blot und immuncytochemistry demonstrated a significant reduced NIPP1 expression by incubation of podocytes with AGE-BSA. The decrease in NIPP1 protein promotes a stimulated activity of PP1. The meaning of in vitro data was confirmed in vivo. Immuncytochemistry demonstrated a significant reduced NIPP1 expression in the podocytes of diabetic mice compared with the non-diabetic control. Blocking RAGE revealed that AGE/RAGE interaction is responsible for the observed suppression of NIPP1. Transfection of podocytes with NIPP1 siRNA caused a significant increased activity of NFB. The impact of NIPP1 suppression for the pathophysiological consequences induced by AGE in podocytes was analyzed by transfection of cells with NIPP1 siRNA. These studies showed that down-regulation of NIPP1 stimulated an increased protein expression of p27Kip1 and the arrest of podocytes in G0/G1 phase associated with a hypertrophic phenotype of podocytes, a typical alteration in early diabetic nephropathy. In summary the results emphasize an AGE/RAGE dependent suppression of NIPP1 in podocytes in association with an increased PP1 activity.

Zitieren

Zitierform:

Liebisch, Marita: Der Einfluss von advanced glycation end-products auf die podozytäre Expression des nuklearen Inhibitors der Proteinphosphatase 1. 2014.

Zugriffsstatistik

Gesamt:
Volltextzugriffe:
Metadatenansicht:
12 Monate:
Volltextzugriffe:
Metadatenansicht:

Grafik öffnen

Export