Chondroitin 4‐sulphate exhibits inhibitory effect during Cu<sup>2+</sup>‐mediated LDL oxidation

Albertini, Riccardo; Ramos, Pilar; Gießauf, Andreas; Passi, Alberto; Luca, Giancarlo De; Esterbauer, Hermann

doi:10.1016/s0014-5793(97)00043-4

Cited by 41 publications

(25 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Chondroitin 4-sulfate inhibited the cytoadherence of P. falciparum-infected erythrocytes to melanoma cells, whereas chondroitin 6-sulfate had little or no effect (38). Chondroitin 4-sulfate, but not chondroitin 6-sulfate, exhibited an inhibitory effect during Cu 2ϩ -mediated low density lipoprotein oxidation (39). Chondroitin 6-sulfate inhibited neurite growth from rat cerebellar and dorsal root ganglion neurons, whereas chondroitin 4-sulfate stimulated elongation of dorsal root ganglion neurites (40).…”

Section: Discussionmentioning

confidence: 95%

Purification and Characterization of Chondroitin 4-Sulfotransferase from the Culture Medium of a Rat Chondrosarcoma Cell Line

Yamauchi

Hirahara

Usui

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

Chondroitin 4-sulfotransferase, which transfers sulfate from 3-phosphoadenosine 5-phosphosulfate to position 4 of N-acetylgalactosamine in chondroitin, was purified 1900-fold to apparent homogeneity with 6.1% yield from the serum-free culture medium of rat chondrosarcoma cells by affinity chromatography on heparin-Sepharose CL-6B, Matrex gel red A-agarose, 3,5-ADP-agarose, and the second heparin-Sepharose CL-6B. SDS-polyacrylamide gel electrophoresis of the purified enzyme showed two protein bands. Molecular masses of these protein were 60 and 64 kDa under reducing conditions and 50 and 54 kDa under nonreducing conditions. Both the protein bands coeluted with chondroitin 4-sulfotransferase activity from Toyopearl HW-55 around the position of 50 kDa, indicating that the active form of chondroitin 4-sulfotransferase is a monomer. Dithiothreitol activated the purified chondroitin 4-sulfotransferase. The purified enzyme transferred sulfate to chondroitin and desulfated dermatan sulfate. Chondroitin sulfate A and chondroitin sulfate C were poor acceptors. Chondroitin sulfate E from squid cartilage, dermatan sulfate, heparan sulfate, and completely desulfated N-resulfated heparin hardly served as acceptors of the sulfotransferase. The transfer of sulfate to the desulfated dermatan sulfate occurred preferentially at position 4 of the N-acetylgalactosamine residues flanked with glucuronic acid residues on both reducing and nonreducing sides.Chondroitin sulfate proteoglycan is found in various tissues and thought to play important roles in various cellular interactions involving cell adhesion (1, 2), regulation of neurite outgrowth (3-6), migration of neural crest cells (7), binding of phospholipase A 2 (8), and an adherence receptor for Plasmodium falciparum-infected erythrocytes (9). In most of mammalian and avian chondroitin sulfate proteoglycans, the glycosaminoglycan chains bear sulfate at position 4 or 6 of N-acetylgalactosamine residues. The ratio of chondroitin 4-sulfate/chondroitin 6-sulfate has been reported to vary with the development of animals (10 -12), malignant change (13), and leukocyte differentiation (14). Sulfation of positions 4 and 6 of GalNAc residue was shown to be catalyzed by different sulfotransferases (15); chondroitin 4-sulfotransferase (C4ST) 1 and chondroitin 6-sulfotransferase (C6ST). Characterization of the purified sulfotransferases and molecular cloning of these cDNAs are basically important to reveal the functional roles of these chondroitin sulfate isomers. We have purified C6ST from the culture medium of chick chondrocytes (16) and cloned the cDNA (17). Unexpectedly, the purified C6ST was found to catalyze not only chondroitin but also keratan sulfate (18) and sialyl N-acetyllactosamine oligosaccharides (19). We previously observed that C4ST was also secreted to the culture medium of chick chondrocytes (20), but the purification of C4ST from the culture medium of chick chondrocytes has been hampered by the presence of an excess amount of C6ST. Unlike chick chondrocytes, rat chondrosa...

show abstract

Section: Discussionmentioning

confidence: 95%

Purification and Characterization of Chondroitin 4-Sulfotransferase from the Culture Medium of a Rat Chondrosarcoma Cell Line

Yamauchi

Hirahara

Usui

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It has been shown that 6-sulfated CS increases the susceptibility of lipoproteins to oxidized in vitro (Camejo et al, 1998). In contrast, 4-sulfated CS exhibits anti-atherogenic properties, since it prevents Cu 2+ induced LDL and HDL oxidation (Albertini, et al, 1997.…”

Section: Introductionmentioning

confidence: 99%

Versican undergoes speciﬁc alterations in the ﬁne molecular structure and organization in human aneurysmal abdominal aortas

Theocharis

Tsolakis

Hjerpe

et al. 2003

Biomedical Chromatography

View full text Add to dashboard Cite

Versican is the major matrix proteoglycan in aortic wall and participates in various biological functions of the tissue. In the present study the molecular characteristics of versican isolated from normal human aorta as well as those of versican expressed in aneurysmal aortic tissue were examined. Versican was isolated by combined anion-exchange and gel permeation chromatography and was further characterized by high-performance liquid chromatography, polyacrylamide gel electrophoresis and immunoblotting. In both tissues versican is exclusively substituted with chondroitin sulfate chains, in contrast to other human tissues where both chondroitin and dermatan sulfate chains are attached onto versican core proteins. Except for the significant decrease in the concentration of versican in the aneurysmal tissue, this PG undergoes specific alterations in the aneurysmal tissue. The molecular size of versican isolated from diseased tissue is decreased with a simultaneous increase in the ratio of glycosaminoglycan to protein in this tissue. The latter reflect the extensive fragmentation of versican in the diseased tissue and most probably the generation of shorter peptides enriched to glycosaminoglycan chains. Although the size of chondroitin sulfate chains is identical in both versican preparations, a significant increase in the percentage of 6-sulfated disaccharides is observed in chondroitin sulfate chains of versican in aneurysmal aortas, which is accompanied by decrease in 4-sulfated and non-sulfated units.

show abstract

“…These molecules may be distinguishable as a function of their degree of sulphation at the C-4 or C-6 positions of galactosamine. C4S exhibited the greatest antioxidant effect among CS (Campo et al, 2004b;Albertini et al, 1997).…”

Section: Discussionmentioning

confidence: 94%

NF‐kB and caspases are involved in the hyaluronan and chondroitin‐4‐sulphate‐exerted antioxidant effect in fibroblast cultures exposed to oxidative stress

Campo

Avenoso

Campo

et al. 2007

J of Applied Toxicology

View full text Add to dashboard Cite

Oxidative stress, inflammation and apoptosis play a critical role in the onset and progression of cellular damage. It was previously reported that hyaluronan (HA) and chondroitin-4-sulphate (C4S) were able to protect human skin fibroblasts from oxidative stress. This antioxidant activity is due to the chelation of transition metal ions. Nuclear factor kB (NF-kB), complexed with the inhibitory protein IkB alpha, is an ubiquitous response transcription factor involved in inflammatory reactions and acts by inducing cytokine expression, chemokines and cell adhesion molecules. Caspases are specific proteases responsible for the regulation and the execution of apoptotic cell death. The damage caused by free radicals may be amplified greatly by the activation of these factors. The study investigated whether the ability of these glycosaminoglycans (GAGs) to reduce oxidative damage in fibroblast cultures involves NF-kB and caspases modulation. The treatment of fibroblasts with both HA and C4S limited the cell damage induced by FeSO(4) plus ascorbate. An interesting aspect of this treatment was that these GAGs significantly inhibited NF-kB DNA binding, as confirmed by the normalization of IkB alpha protein, and reduced caspase activation at both mRNA and protein level. A possible explanation for these results, since lipid peroxidation intermediates may induce NF-kB and caspase activation, is that HA and C4S indirectly blocked NF-kB DNA binding and apoptosis by inhibiting reactive oxygen species (ROS) production. These data suggest that, during oxidative stress, HA and C4S may reduce cell damage by inhibiting NF-kB and apoptosis activation as well as protecting cells from free radical attack. According to these finding the use of HA and C4S could be positive both as tool to clarify the exact mechanism of GAGs/ROS interaction, and also as drug therapy to reduce oxidative stress during inflammation.

show abstract

Chondroitin 4‐sulphate exhibits inhibitory effect during Cu²⁺‐mediated LDL oxidation

Cited by 41 publications

References 19 publications

Purification and Characterization of Chondroitin 4-Sulfotransferase from the Culture Medium of a Rat Chondrosarcoma Cell Line

Purification and Characterization of Chondroitin 4-Sulfotransferase from the Culture Medium of a Rat Chondrosarcoma Cell Line

Versican undergoes speciﬁc alterations in the ﬁne molecular structure and organization in human aneurysmal abdominal aortas

NF‐kB and caspases are involved in the hyaluronan and chondroitin‐4‐sulphate‐exerted antioxidant effect in fibroblast cultures exposed to oxidative stress

Contact Info

Product

Resources

About

Chondroitin 4‐sulphate exhibits inhibitory effect during Cu2+‐mediated LDL oxidation

Cited by 41 publications

References 19 publications

Purification and Characterization of Chondroitin 4-Sulfotransferase from the Culture Medium of a Rat Chondrosarcoma Cell Line

Purification and Characterization of Chondroitin 4-Sulfotransferase from the Culture Medium of a Rat Chondrosarcoma Cell Line

Versican undergoes speciﬁc alterations in the ﬁne molecular structure and organization in human aneurysmal abdominal aortas

NF‐kB and caspases are involved in the hyaluronan and chondroitin‐4‐sulphate‐exerted antioxidant effect in fibroblast cultures exposed to oxidative stress

Contact Info

Product

Resources

About

Chondroitin 4‐sulphate exhibits inhibitory effect during Cu²⁺‐mediated LDL oxidation