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Purification and characterization of mouse soluble receptor for advanced glycation end products (sRAGE)
Lana E Hanford1, Jan J Enghild, Zuzana Valnickova
1Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
Abstract:
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.
Insights
Soluble RAGE (sRAGE) acts as a decoy to prevent disease progression. Mouse sRAGE is biochemically characterized and differs from human sRAGE, likely produced by truncation, not splicing.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Receptor for advanced glycation end products (RAGE) is implicated in diseases like cancer and Alzheimer's.
- The secreted isoform, soluble RAGE (sRAGE), acts as a decoy to inhibit RAGE signaling.
- Human sRAGE is produced via alternative mRNA splicing.
Purpose of the Study:
- To determine the production mechanism of mouse sRAGE.
- To biochemically characterize mouse sRAGE, including glycosylation and disulfide patterns.
- To investigate sRAGE binding to heparin.
Main Methods:
- Biochemical characterization of mouse sRAGE.
- Analysis of glycosylation and disulfide patterns.
- Heparin binding assays.
Main Results:
- Mouse sRAGE is likely produced by carboxyl-terminal truncation, unlike human sRAGE.
- Biochemical characterization revealed specific glycosylation and disulfide patterns.
- Mouse sRAGE demonstrated binding to heparin, suggesting a role in extracellular matrix distribution.
Conclusions:
- Mouse sRAGE production mechanism differs from humans.
- Biochemical properties of mouse sRAGE provide insights into its function.
- Heparin binding suggests a role for sRAGE in tissue distribution and RAGE signaling modulation.
