Do ASARM peptides play a role in nephrogenic systemic fibrosis?

American Journal of Physiology. Renal Physiology
Peter S N RoweEllen T McCarthy

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 Ca2+ and hydroxyapatite. Since the ionic radius of Gd3+ is close to that of Ca2+, we hypothesized that ASARM peptides increase the risk of NSF by inducing release of Gd3+ from GBCAs. Here, we show 1) ASARM peptides bind and induce release of Gd3+ from GBCAs in vitro and in vivo; 2) A bioengineered peptide (SPR4) stabilizes the Gd3+-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA-induced NSF-l...Continue Reading

References

Oct 21, 2006·Current Opinion in Rheumatology·Anjela GalanRichard Bucala
Sep 15, 2007·Radiology·Emanuel KanalHenrik S Thomsen
Jul 4, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·William N AddisonMarc D McKee
Oct 5, 2010·Analytical and Bioanalytical Chemistry·Danielle ClevelandAnil K Patri
Dec 24, 2010·American Journal of Physiology. Renal Physiology·Valentin DavidPeter S N Rowe
Jul 12, 2011·British Journal of Pharmacology·N FretellierC Corot
Feb 22, 2012·Critical Reviews in Eukaryotic Gene Expression·Peter S N Rowe
Sep 20, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nilana M T BarrosMarc D McKee
Sep 27, 2014·Critical Reviews in Toxicology·Jean-Marc IdéeClaire Corot
Dec 3, 2014·Bone·Lesya V ZelenchukPeter S N Rowe

❮ Previous
Next ❯

Citations

Oct 19, 2017·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Joel GarciaAngelique Y Louie

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Jeffrey G Penfield
Clinical Journal of the American Society of Nephrology : CJASN
Mark A Perazella
© 2021 Meta ULC. All rights reserved