Jump to ContentJump to Main Navigation
Show Summary Details
In This Section

Interdisciplinary Toxicology

The Journal of Institute of Experimental Pharmacology of Slovak Academy of Sciences

4 Issues per year

CiteScore 2016: 1.43

SCImago Journal Rank (SJR) 2015: 0.518
Source Normalized Impact per Paper (SNIP) 2015: 0.897

Open Access
See all formats and pricing
In This Section

Catabolism of hyaluronan: Involvement of transition metals

Ladislav Šoltés
  • Institute of Experimental Pharmacology, Slovak Academy of Sciences, SK-84104 Bratislava, Slovakia
/ Grigorij Kogan
  • Directorate Health, Directorate General Research, European Commission, B-1049, Brussels, Belgium
Published Online: 2010-01-06 | DOI: https://doi.org/10.2478/v10102-009-0026-y

Catabolism of hyaluronan: Involvement of transition metals

One of the very complex structures in the vertebrates is the joint. The main component of the joint is the synovial fluid with its highmolar-mass glycosaminoglycan hyaluronan, which turnover is approximately twelve hours. Since the synovial fluid does not contain any hyaluronidases, the fast hyaluronan catabolism is caused primarily by reductive-oxidative processes.

Eight transition metals - V23, Mn25, Fe26, Co27, Ni28, Cu29, Zn30, and Mo42 - naturally occurring in living organism are essential for the control of various metabolic and signaling pathways. They are also the key elements in catabolism of hyaluronan in the joint.

In this overview, the role of these metals in physiological and pathophysiological catabolism of hyaluronan is described. The participation of these metals in the initiation and propagation of the radical degradation hyaluronan is critically reviewed.

Keywords: hyaluronan catabolism; synovial fluid; joint; transition metals; peroxidation; oxidative stress

  • Buettner GR, Jurkiewicz BA. (1993). The ascorbate free radical as a marker of oxidative stress: An EPR study. Free Radic Biol Med 14: 49-55.

  • Delmage JM, Powars DR, Jaynes PK, Allerton SE. (1986). The selective suppression of immunogenicity by hyaluronic acid. Annals of Clinical and Laboratory Science 16: 303-310.

  • Feinberg RN, Beebe DC. (1983). Hyaluronate in vasculogenesis. Science 220: 1177-1179.

  • Fisher AEO, Naughton DP. (2003). Vitamin C contributes to inflammation via radical generating mechanisms: a cautionary note. Medical Hypotheses 61: 657-660.

  • Fisher AEO, Naughton DP. (2004). Iron supplements: the quick fix with longterm consequences. Nutrition Journal 3: 1-5.

  • Fisher AEO, Naughton DP. (2005). Therapeutic chelators for the twenty first Century: new treatments for iron and copper mediated inflammatory and neurological disorders. Current Drug Delivery 2: 261-268. [Crossref] [PubMed]

  • Flemmig J, Arnhold J. (2007). Ferrous ion-induced strand breaks in the DNA plasmid pBR322 are not mediated by hydrogen peroxide. Eur Biophys J 36: 377-384. [Web of Science]

  • Gaetke LM, Chow CK. (2003). Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 189: 147-163.

  • Grootveld M, Henderson EB, Farrell A, Blake DR, Parkes HG, Haycock P. (1991). Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r. spectroscopy. Biochem J 273: 459-467.

  • Halliwell B, Gutteridge JMC. (1990). Role of free radicals and catalytic metal ions in human disease: An overview. Methods Enzymol 186: 1-85.

  • HaMai D, Bondy SC, Becaria A, Campbell A. (2001). The chemistry of transition metals in relation to their potential role in neurodegenerative processes. Curr. Topics Med. Chem. 1: 541-551.

  • Hardingham T. (2004). Solution Properties of Hyaluronan, in Chemistry and Biology of Hyaluronan (Garg HG and Hales CA eds) pp. 1-19, Elsevier Press, Amsterdam.

  • Hawkins CL, Davies MJ. (1996). Direct detection and identification of radicals generated during the hydroxyl radical-induced degradation of hyaluronic acid and related materials. Free Radicals in Biology and Medicine 21(3): 275-290.

  • Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, Shinomura T, Hamaguchi M, Yoshida Y, Ohnuki Y, Miyauchi S, Spicer AP, McDonald JA, Kimata K. (1999). Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem 274: 25085-25092.

  • Jiang D, Liang J, Noble PW. (2007). Hyaluronan in Tissue Injury and Repair. Annual Review of Cell and Developmental Biology 23: 435-461. [Web of Science]

  • Khan MMT, Martell AE. (1967). Metal ion and metal chelate catalyzed oxidation of ascorbic acid by molecular oxygen. I. Cupric and ferric ion catalyzed oxidation. J. Am. Chem. Soc. 89: 4176-4185.

  • Kogan G, Šoltés L, Stern R, Mendichi R. (2007). Chapter 31: Hyaluronic Acid: A Biopolymer with Versatile Physico-Chemical and Biological Properties, in Handbook of Polymer Research: Monomers, Oligomers, Polymers and Composites (Pethrick RA, Ballada A, Zaikov GE eds), pp. 393-439, Nova Science Publishers, New York.

  • Kogan G, Šoltés L, Stern R, Schiller J, Mendichi R. (2008). Hyaluronic Acid: Its Function and Degradation in In Vivo Systems, in Studies in Natural Products Chemistry (Vol. 34 Bioactive Natural Products, Part D) (Atta-ur-Rahman ed) pp. 789-882, Elsevier, Amsterdam.

  • Koppenol WH. (1994). Chemistry of Iron and Copper in Radical Reactions in Free Radical Damage and Its Control (Rice-Evans CA and Burdon RH eds) pp. 3-24, Elsevier Science B.V., Amsterdam.

  • Magnani A, Silvestri V, Barbucci R. (1999). Hyaluronic acid and sulphated hyaruronic acid in aqueous solution: effect of the sulphation in the polyelectrolyte behaviour and complex formation with Cu2+ and Zn2+ ions. Macromolecular Chemistry and Physics 200: 2003-2014.

  • McBride WH, Bard JB. (1979). Hyaluronidase-sensitive halos around adherent cells. Their role in blocking lymphocyte-mediated cytolysis. Journal of Experimental Medicine 149: 507-515.

  • Myint P, Deeble DH, Beaumont PC, Blake SM, Phyllips GO. (1987). The reactivity of various free radicals with hyaluronic acid: steady-state and pulse radiolysis studies, Biochim Biophys Acta 925: 194-202.

  • Niedermeier W, Griggs JH. (1971). Trace metal composition of synovial fluid and blood serum of patients with rheumatoid arthritis. J Chronic Dis 23: 527-536.

  • Noble PW. (2002). Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biology 21: 25-29.

  • Pirc ET, Arčcon I, Kodre A, Bukovec P. (2004). Metal-ion environment in solid Mn(II), Co(II) and Ni(II) hyaluronates. Carbohydrate Research 339: 2549-2554.

  • Presti D, Scott JE. (1994). Hyaluronan-mediated protective effect against cell damage caused by enzymatically produced hydroxyl (OH·) radicals is dependent on hyaluronan molecular mass. Cell Biochemistry and Function 12: 281-288.

  • Qian SY., Buettner GR. (1999). Iron and dioxygen chemistry is an important route to initiation of biological free radical oxidations: An electron paramagnetic resonance spin trapping study. Free Radicals in Biology and Medicine 26: 1447-1456.

  • Roth JA. (2006). Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination. Biological Research 39: 45-57.

  • Rychlý J, Šoltés L, Stankovská M, Janigová I, Csomorová K, Sasinková V, Kogan G, Gemeiner P. (2006). Unexplored capabilities of chemiluminescence and thermoanalytical methods in characterization of intact and degraded hyaluronans. Polym Degrad Stabil 91: 3174-3184.

  • Shukla N, Maher J, Masters J, Angelini GD, Jeremy JY. (2006). Does oxidative stress change ceruloplasmin from a protective to a vasculopathic risk factor? Atherosclerosis 187: 238-250.

  • Šoltés L, Kogan G, Stankovská M, Mendichi R, Rýchly J, Schiller J, Gemeiner P. (2007). Degradation of high-molecular-mass hyaluronan and characterization of fragments. Biomacromolecules 8: 2697-2705. [Web of Science]

  • Šoltés L, Mendichi R, Kogan G, Schiller J, Stankovská M, Arnhold J. (2006). Degradative action of reactive oxygen species on hyaluronan. Biomacromolecules 7: 659-668.

  • Šoltés L, Stankovská M, Brezová V, Schiller J, Arnhold J, Kogan G, Gemeiner P. (2006). Degradation of high-molecular-weight hyaluronan by hydrogen peroxide in the presence of cupric ions. Carbohydrate Research 341: 2826-2834.

  • Šoltés L, Valachová K, Mendichi R, Kogan G, Arnhold J, Gemeiner P. (2007). Solution properties of high-molar-mass hyaluronans: the biopolymer degradation by ascorbate. Carbohydrate Research 342: 1071-1077. [Web of Science]

  • Stern R, Asari AA, Sugahara KN. (2006), Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85(8): 699-715.

  • Stern R, Kogan G, Jedrzejas MJ, Šoltés L. (2007). The many ways to cleave hyaluronan. Biotechnol Adv 25: 537-557. [Web of Science]

  • Szilagyi RK, Bryngelson PA, Maroney MJ, Hedman B, Hodgson KO, Solomon EI. (2004). S K-edge C-ray absorption spectroscopic investigation of the Ni-containing superoxide dismutase active site. J Am Chem Soc 126: 3018-3019.

  • Thornalley PJ. (2003). Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy. Biochemical Society Transactions 31: 1343-1348.

  • Udenfriend S, Clark CT, Axelrod J, Brodie BB. (1954). Ascorbic acid in aromatic hydroxylation. I. A model system for aromatic hydroxylation. Journal of Biological Chemistry 208: 731-739.

  • Valachova K, Kogan G, Gemeiner P, Soltes L. (2009). Hyaluronan degradation by ascorbate: Protective effects of manganese(II) chloride, in Kinetics & Thermodynamics for Chemistry & Biochemistry: Vol. 2 (Pearce EM, Zaikov GE, Kirshenbaum G eds), pp. 201-215, Nova Science Publishers, New York.

  • Valko M, Morris H, Cronin MTD. (2005). Metals, Toxicity and Oxidative Stress. 12: 1161-1208.

  • Weigel PH, DeAngelis PL. (2007). Hyaluronan Synthases: A Decade-plus of Novel Glycosyltransferases J Biol Chem 282: 36777-36781. [Web of Science]

  • Weissberger A, LuValle JE, Thomas DS Jr. (1943). Oxidation processes. XVI. The autooxidation of ascorbic acid. Journal of American Chemical Society 65: 1934-1939.

  • West DC, Hampson IN, Arnold F, Kumar S. (1985). Angiogenesis induced by degradation products of hyaluronic acid. Science 228: 1324-1326.

  • Wong SF, Halliwell B, Richmond R, Skowroneck WR. (1981). The role of superoxide and hydroxyl radicals in the degradation of hyaluronic acid induced by metal ions and by ascorbic acid. J Inorg Biochem 14: 127-134.

About the article

Published Online: 2010-01-06

Published in Print: 2009-12-01

Citation Information: Interdisciplinary Toxicology, ISSN (Online) 1337-9569, ISSN (Print) 1337-6853, DOI: https://doi.org/10.2478/v10102-009-0026-y. Export Citation

This content is open access.

Comments (0)

Please log in or register to comment.
Log in