Structure Elucidation of a Senescence Cross-Link from Human Extracellular Matrix

The unexpected discovery of pentose-mediated protein cross-linking raises new questions concerning the aging process and suggests ribose or ribonucleotide metabolites as precursors.

Abstract

Isolation and structure elucidation of an acid-resistant fluorescent molecule from human extracellular matrix revealed the presence of an imidazo[4,5-b]pyridinium molecule comprising a lysine and an arginine residue cross-linked by a pentose. Structure confirmation was achieved in vitro by the nonenzymatic reaction of ribose with lysine and arginine residues. The cross-link, named pentosidine, could also be synthesized with isomers of ribose, arabinose, xylose, and lyxose as well as by incubating young human collagen with these sugars at 37 degrees C. Pentosidine was found in a variety of human tissues including plasma proteins and red blood cells. Its presence in cells grown in culture strongly suggests ribose or ribonucleotide metabolites as precursors. The unexpected discovery of pentose-mediated protein cross-linking raises new questions concerning the aging process.