Inhibitory Effect of Peptide-Free Forms of Advanced Glycation End Products on the Proliferation and Extracellular Matrix Protein Production of Cultured Cells

Abstract

Advanced glycation end products (AGEs), generated by the Maillard reaction, accumulate in long-lived proteins like collagen and are presumed to be involved in aging and the pathogenesis of complications in diabetes. We investigated the effect of peptide-free forms of AGEs that can be released by the catabolism of AGE-proteins on cellular activities using cultured cells and synthetic AGEs, pentosidine and pyrraline. The exposure of cultured fibroblasts to 15 or 30 μM of pentosidine resulted in the partial inhibition of cell proliferation and production of extracellular matrix (ECM) proteins. Pentosidine also inhibited the proliferation and ECM protein production of chondrocytes, but its effect on cell proliferation was weak while that on ECM production was prominent, as compared with the effect of pentosidine. A similar inhibitory effect on cell proliferation was observed when fibroblasts or chondrocytes were exposed to pyrraline. Pentosidine and pyrraline did not cause cell death in these cells. Pentosidine appeared to enter the cells during the culture. These results suggest that peptide-free forms of AGEs affect cell growth and cell metabolism by acting both extracellularly and intracellularly.