A comparative study of sulphated polysaccharide effects on advanced glycation end-product uptake and scavenger receptor class A level in macrophages

Abstract

Advanced glycation end-products, especially toxic advanced glycation end-products derived from glyceraldehyde (advanced glycation end-product-2) and glycolaldehyde (advanced glycation end-product-3), are biologically reactive compounds associated with diabetic complications. We previously demonstrated that toxic advanced glycation end-products were internalised into macrophage-like RAW264.7 cells through scavenger receptor-1 class A (CD204). Toxic advanced glycation end-product uptake was inhibited by fucoidan, a sulphated polysaccharide and antagonistic ligand for scavenger receptors, suggesting that sulphated polysaccharides are emerging candidates for treatment of advanced glycation end-product-related diseases. In this study, we compared the effects of six types of sulphated and non-sulphated polysaccharides on toxic advanced glycation end-product uptake in RAW264.7 cells. Fucoidan, carrageenan and dextran sulphate attenuated toxic advanced glycation end-product uptake. Fucoidan and carrageenan inhibited advanced glycation end-product-2-induced upregulation of SR-A, while advanced glycation end-product-3-induced upregulation of scavenger receptor-1 class A was only suppressed by fucoidan. Dextran sulphate did not affect scavenger receptor-1 class A levels in toxic advanced glycation end-product-treated cells. Chondroitin sulphate, heparin and hyaluronic acid failed to attenuate toxic advanced glycation end-product uptake. Heparin and hyaluronic acid had no effect on scavenger receptor-1 class A levels, while chondroitin sulphate inhibited advanced glycation end-product-3-induced upregulation of scavenger receptor-1 class A. Taken together, fucoidan and carrageenan, but not the other sulphated polysaccharides examined, had inhibitory activities on toxic advanced glycation end-product uptake and toxic advanced glycation end-product-induced upregulation of scavenger receptor-1 class A, possibly because of structural differences among sulphated polysaccharides.