The stuff which sticks cells together (and prevents metastatic process)

Dr. Weeks’ Comment:  Hyaluronan and hyaluronic acid and hyaluronidase all amaze and instruct as regards cancer and the cellular barriers which attempt to control it. The treasures of highly potent biochemicals are frequently enmeshed with venoms. Hyaluronan has been implicated in cancer prevention. We find this valuable agent in bee venom (see below) but also available in a far more comfortable format with oral or topical BioCell Collagen and other highly absorbable forms of this rich natural agent.

 

J Allergy Clin Immunol. 1975 May;55(5):285-98.

Comparison of honeybee venoms and their components from various sources.

Abstract

The use of honeybee venoms and their components may assist in the elucidation of the pathophysiology of reactions to honeybee stings. This initial study compared venoms from various sources by chemical and biological assays, and significant variations were observed. Ten different bee venoms were compared by nitrogen analysis, mouse toxicity, hyaluronidase content, and antigenicity. Based on mouse toxicity, hyaluronidase content, and gel diffusion analysis, two groups of bee venoms could be differentiated. Venoms in one group, Group A, were more toxic, contained hyaluronidase, and showed an additional precipitin band. All venoms contained mellitin as a major fraction, which formed nonimmune precipitin bands during gel diffusion analysis. Gel filtration chromatography and dialysis separated the venoms into components that were then identified by enzyme assays, rat mast cell degranulation, hemolytic activity, and gel diffusion analysis. The venoms within Group A showed similar components, some of which, most noticeably hyaluronidase, were not present in Group B. Dialysis showed that a large portion of the venom could pass through a cellophane membrane including a portion of the phospholipase A. Heterogeneous molecular weights were found for phospholipase A by both gel filtration and dialysis, and may reflect variation in carbohydrate content. It appears that bee venom variability for whatever reason, a heterogeneous MW antigen, and a non-immune precipitable component require careful consideration in any study involving this venomm. These studies have yielded relatively pure, identified bee venom components which can be employed in further studies investigating reactions to honeybee stings.

1.

Protein Sci. 1995 Sep;4(9):1666-9.

Hyaluronidases–a group of neglected enzymes.

Kreil G.

Source

Institute of Molecular Biology, Austrian Academy of Sciences, Salzburg, Austria.

Abstract

Hyaluronan is an important constituent of the extracellular matrix. This polysaccharide can be hydrolyzed by various hyaluronidases that are widely distributed in nature. The structure of some bacterial and animal enzymes of this type has recently been elucidated. It could be shown that the hyaluronidases from bee and hornet venom and the PH-20 hyaluronidase present on mammalian spermatozoa are homologous proteins.

 

2.

Int Arch Allergy Immunol. 2011;156(2):205-11. doi: 10.1159/000322847. Epub 2011 May 19.

Hyaluronidase and hyaluronan in insect venom allergy.

King TP, Wittkowski KM.

Source

The Rockefeller University, New York, NY 10021, USA. kingtp @ rockefeller.edu

Abstract

BACKGROUND:

Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice.

CONCLUSION:

Hyaluronidase by its action on HA in skin can function indirectly as adjuvant to promote IgE and IgG1 response in mice. Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people.

 

3.

Biochemistry. 2007 Jun 12;46(23):6911-20. Epub 2007 May 16.

Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis.

Chao KL, Muthukumar L, Herzberg O.

Source

Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA.

Abstract

Mammalian hyaluronidases hydrolyze hyaluronan, a polysaccharide of diverse physiological roles found in all tissues and body fluids. In addition to its function in normal cellular hyaluronan turnover, human hyaluronidase-1 is implicated in cancer proliferation, angiogenesis, and inflammatory diseases; its expression is up-regulated in advanced stages of bladder cancer, whereas the expression of the alternative splice-variants is down-regulated. The crystal structure reveals a molecule composed of two closely associated domains: a catalytic domain that adopts a distorted (beta/alpha)8 barrel resembling that of bee venom hyaluronidase, and a novel, EGF-like domain, characteristic of involvement in protein-protein interactions and regulatory processes. The structure shows that the fold of this unique EGF-like domain is intact in four alternative splice-variants, whereas the catalytic domain is likely to be unfolded. Thus, these variants may function by competing with the full-length enzyme for the putative protein partner and regulating enzymatic activity in healthy cells.

 

4.

Structure. 2000 Oct 15;8(10):1025-35.

Crystal structure of hyaluronidase, a major allergen of bee venom.

Marković-Housley Z, Miglierini G, Soldatova L, Rizkallah PJ, Müller U, Schirmer T.

Source

Division of Structural Biology Biozentrum University of Basel CH-4056, Basel, Switzerland. zora.housley@unibas.ch

Abstract

BACKGROUND:

Hyaluronic acid (HA) is the most abundant glycosaminoglycan of vertebrate extracellular spaces and is specifically degraded by a beta-1,4 glycosidase. Bee venom hyaluronidase (Hya) shares 30% sequence identity with human hyaluronidases, which are involved in fertilization and the turnover of HA. On the basis of sequence similarity, mammalian enzymes and Hya are assigned to glycosidase family 56 for which no structure has been reported yet.

CONCLUSIONS:

The structure of the complex strongly suggest an acid-base catalytic mechanism, in which Glu113 acts as the proton donor and the N-acetyl group of the substrate is the nucleophile. The location of the catalytic residues shows striking similarity to bacterial chitinase which also operates via a substrate-assisted mechanism.

 

5.

Anal Biochem. 1984 Nov 15;143(1):76-81.

Hyaluronidase polymorphism detected by polyacrylamide gel electrophoresis. Application to hyaluronidases from bacteria, slime molds, bee and snake venoms, bovine testes, rat liver lysosomes, and human serum.

Fiszer-Szafarz B.

 

Abstract

A gel electrophoretic technique which allows detection of hyaluronidase activity in the gel has been devised. The principle is that the high-molecular-weight substrate, hyaluronic acid, is included in the gel, where it cannot move in the electrical field. After the run, the gel is incubated under conditions allowing the enzyme to degrade the substrate. Upon staining with “Stains-all” dye (Eastman Kodak Co., 2718), zones of hyaluronidase activity appear as pink bands in a blue background. The sensitivity limit is less than 3 fkat equivalent to 2.2 NF mU. The method is applicable to all types of hyaluronidases and chondroitinase ABC. It enabled to be shown that some hyaluronidases are polymorphic. This technique also made it possible to detect easily hyaluronidase activity in normal human serum. This analytical method represents a convenient step in the purification of hyaluronidase.

 

Post Comment