Discrete binding patterns of two heparin-reactive proteins, basic fibroblast growth factor and peptide p5R, in amyloid-laden and healthy mice.

Emily B Martin, Robert Donnell, Tina Richey, Alan Stuckey, Stephen J Kennel, Jonathan S Wall

Biochemical and biophysical research communications 2021 May 07

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Peptide p5R is a synthetic, polybasic, heparin-binding peptide that preferentially reacts with amyloid deposits in vivo and in tissue sections. Basic fibroblast growth factor (bFGF1) similarly interacts with heparin-like molecules, notably heparan sulfate proteoglycans (HSPG), in the extracellular matrix and on cell surfaces. The aim of this study was to compare the biodistribution of p5R and bFGF in healthy mice as well as those with systemic inflammation-associated amyloidosis (AA), which contains HSPG, by using SPECT/CT imaging, tissue biodistribution measurements and micro-autoradiography. Although both proteins are known to bind heparan sulfate, their biodistribution was remarkably different in the healthy and diseased animals. Imaging revealed uptake of both radiolabeled proteins in the liver, spleen, and kidneys of mice with amyloidosis; however, 125I-bFGF, but not 125I-p5R, was observed in normal tissue at sites of HSPG expression, including the hepatic and splenic sinusoids and renal glomerulae. Microautoradiography demonstrated that while p5R bound exclusively to amyloid deposits in the spleen and liver of AA mice, bFGF had a broader binding pattern. Consequently, even though bFGF and p5R both interact with heparan sulfate moieties, p5R binding was restricted to HSPG in amyloid deposits and did not bind HSPG in healthy tissues, whereas bFGF preferentially reacted with HSPG in normal tissue. The data suggest that peptide p5R selectively binds HSPG in amyloid and that the HSPG in healthy tissue, recognized by bFGF, is not targeted by the peptide. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Emily B Martin, Robert Donnell, Tina Richey, Alan Stuckey, Stephen J Kennel, Jonathan S Wall. Discrete binding patterns of two heparin-reactive proteins, basic fibroblast growth factor and peptide p5R, in amyloid-laden and healthy mice. Biochemical and biophysical research communications. 2021 May 07;552:136-141