Purification and characterization of mouse soluble receptor for advanced glycation end products (sRAGE).
The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface proteins that has been implicated as a progression factor in a number of pathologic conditions from chronic inflammation to cancer to Alzheimer's disease. In such conditions, RAGE acts to facilitate pathogenic processes. Its secreted isoform, soluble RAGE or sRAGE, has the ability to prevent RAGE signaling by acting as a decoy. sRAGE has been used successfully in animal models of a range of diseases to antagonize RAGE-mediated pathologic processes. In humans, sRAGE results from alternative splicing of RAGE mRNA. This study was aimed to determine whether the same holds true for mouse sRAGE and, in addition, to biochemically characterize mouse sRAGE. The biochemical characteristics examined include glycosylation and disulfide patterns. In addition, sRAGE was found to bind heparin, which may mediate its distribution in the extracellular matrix and cell surfaces of tissues. Finally, our data indicated that sRAGE in the mouse is likely produced by carboxyl-terminal truncation, in contrast to the alternative splicing mechanism reported in humans.
Hanford
Lana E
LE
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
Enghild
Jan J
JJ
Valnickova
Zuzana
Z
Petersen
Steen V
SV
Schaefer
Lisa M
LM
Schaefer
Todd M
TM
Reinhart
Todd A
TA
Oury
Tim D
TD
D017398:Alternative Splicing; D000818:Animals; D002846:Chromatography, Affinity; D008168:Lung / Q000378:metabolism; D051379:Mice; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic