Molecular Signature of Kappa-Carrageenan Mimics Chondroitin-4-Sulfate and Dermatan Sulfate and Enables Interaction with Arylsulfatase B

The common food additive kappa-carrageenan ( -CGN) is a sulfated polysaccharide that resembles chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). All have a sulfate group on C4 of a glycoside (galactose for carrageenan and Nacetylgalactosamine for C4S), and the sulfate-bearing glycoside is linked in a -1,4- configuration to an unsulfated, 6-carbon sugar (galactose for carrageenan, glucuronate for C4S, and iduronate for DS). The enzyme arylsulfatase B (ARSB; N-acetylgalactosamine- 4-sulfate) is the highly selective enzyme that removes the 4-sulfate group from the nonreducing terminus of C4S and DS, thereby regulating subsequent degradation. In this report, -CGN is shown to be a substrate for recombinant human ARSB (rhARSB). Sulfate was generated from both C4S and -CGN following incubation with rhARSB. Exposure of human colonic epithelial cells to -CGN, but not to C4S produced reactive oxygen species (ROS) and increased Interleukin (IL)-8 secretion. The ROS production from -CGN was reduced by exposure to rhARSB, but increased by competition from C4S or DS, but not from chondroitin-6-sulfate (C6S). Prior treatment of either lambda- or iota-CGN with rhARSB had no impact on ROS, IL-8, or inorganic sulfate production, demonstrating a specific effect of the molecular configuration of -CGN. By mimicry of C4S and DS and by interaction with ARSB, -CGN can directly interfere with the normal, cellular functions of C4S, DS, and ARSB. Since C4S and DS are present in high concentration in tissues, the impact of -CGN exposure may be due to some extent by interference with the normal biological functions of ARSB, C4S, and DS.