title: Molecular signature of kappa-carrageenan mimics chondroitin-4-sulfate and dermatan sulfate and enables interaction with arylsulfatase B.
abstract: The common food additive kappa-carrageenan (κ-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 CGN and N-acetylgalactosamine for C4S), and the sulfate-bearing glycoside is linked in a β-1,4-configuration to an unsulfated, six-carbon sugar (galactose for CGN, glucuronate for C4S and iduronate for DS). The enzyme arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfate) is the highly selective enzyme that removes the four-sulfate group from the nonreducing terminus of C4S and DS, thereby regulating subsequent degradation. In this report, κ-CGN is shown to be a substrate for recombinant human ARSB (rhARSB). Sulfate was generated from both C4S and κ-CGN following incubation with rhARSB. Exposure of human colonic epithelial cells to κ-CGN, but not to C4S, produced reactive oxygen species (ROS) and increased interleukin (IL)-8 secretion. The ROS production from κ-CGN was reduced by exposure to rhARSB, but increased by competition from C4S or DS, but not from chondroitin-6-sulfate. 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 κ-CGN. By mimicry of C4S and DS and by interaction with ARSB, κ-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 κ-CGN exposure may be due to some extent to interference with the normal biological functions of ARSB, C4S and DS.
authors.affiliation: Department of Medicine, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Joanne K
authors.initials: JK
authors.lastname: Tobacman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002236:Carbohydrate Conformation; D002351:Carrageenan / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000378:metabolism*; D003092:Colitis / Q000209:etiology / Q000517:prevention & control; D003106:Colon / Q000276:immunology / Q000378:metabolism*; D003164:Competitive Bidding; D003871:Dermatan Sulfate / Q000737:chemistry / Q000378:metabolism*; D005503:Food Additives / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D005524:Food Technology; D006801:Humans; D006868:Hydrolysis; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D018716:Molecular Mimicry; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C508606:CXCL8 protein, human; D005503:Food Additives; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D003871:Dermatan Sulfate; D002351:Carrageenan; D002809:Chondroitin Sulfates; D020051:N-Acetylgalactosamine-4-Sulfatase