Mechanism of increased clearance of glycated albumin by Proximal tubule cells.

Mechanism of increased clearance of glycated albumin by Proximal tubule cells. Am J Physiol Renal Physiol. 2016 Feb 17;:ajprenal.00605.2016 Authors: Wagner MC, Myslinski J, Pratap S, Flores B, Rhodes GJ, Sandoval R, Kumar S, Patel M, Ashish A, Molitoris BA Abstract Serum albumin is the most abundant plasma protein and has a long half-life due to neonatal Fc receptor (FcRn) mediated transcytosis by many cell types including proximal tubule cells of the kidney. Albumin also interacts with, and is modified by, many small and large molecules. Therefore, the focus of this study was to address the impact of specific known biologic albumin modifications on albumin-FcRn binding and cellular handling. Binding at pH 6.0 and 7.4 was performed since FcRn binds albumin strongly at acidic pH and releases it following transcytosis at physiological pH. Equilibrium dissociation constants (KDs) were measured using microscale thermophoresis. Since studies have shown that glycated albumin is excreted in the urine at a higher rate than unmodified albumin we studied glucose and methylgloxal modified albumins (21day). All had reduced affinity to FcRn at pH 6.0 suggesting these albumins would not be returned to the circulation via the transcytotic pathway. To address why modified albumin has reduced affinity we analyzed the structure of the modified albumins using small angle X-ray scattering. This analysis showed significant structural changes occurring to...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research