Do ASARM peptides play a role in Nephrogenic Systemic Fibrosis?

Do ASARM peptides play a role in Nephrogenic Systemic Fibrosis? Am J Physiol Renal Physiol. 2015 Sep 2;:ajprenal.00201.2015 Authors: Rowe PS, Zelenchuk LV, Laurence JS, Lee P, Brooks WM, McCarthy ET Abstract Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium (Gd3(+)) based contrast agents (GBCAs) in patients with kidney disease. The release of toxic Gd3(+) from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of Gd3(+) release from GBCAs is unknown. Increased Acidic Serine Aspartate Rich MEPE Associated peptides (ASARM peptides), induce bone mineralization abnormalities and contribute to renal phosphate-handling defects in inherited hypophosphatemic rickets and tumor-induced osteomalacia. The proteolytic cleavage of related bone matrix proteins with ASARM motifs results in release of ASARM peptide into bone and circulation. ASARM peptides are acidic, reactive, phosphorylated inhibitors of mineralization that bind Ca(2+) and hydroxyapatite. Since the ionic radius of Gd(3+) is close to that of Ca(2+), we hypothesized that ASARM peptides increase risk for NSF by inducing release of Gd(3+) from GBCAs. Here we show: 1) ASARM peptides bind and induce release of Gd(3+) from GBCAs in vitro and in vivo; 2) a bioengineered peptide (SPR4) stabilizes the Gd(3+)-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research