Author Topic: How sugars deal with inflammatory activity and autoimmune diseases  (Read 4634 times)

Offline JC Spencer

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The Laminin Protein Chain and N-acetylneuraminic acid
« Reply #4 on: May 26, 2008, 10:49:02 PM »
Comments by J. C. Spencer
LAMININ has been causing some rather interesting chatter on the internet lately.  Before I heard the chatter, I reported on a paper I wrote in 1996 about the glue that holds the human cells together and without it there is aging, disease, and death. The laminin protein chains give a design that accounts for a lot of its flexibility in connecting up various kinds of molecules.  Because of this, scientists are extremely interested in the whole family of laminins. They are a family of glycoproteins that are an integral part of the structural scaffolding in almost every human cell.

I do not object to the chatter on the internet about laminin and its shape.  Though interesting, I do not get excited about its shape as I do about what it does and how without it we would not know life as we do.  (You can view laminin in our NEWS section under Featured Articles on the Science of Glycomis.)  Of course, its shape is what makes it all hapen.

The abstract below from a science paper out of France shows how the sugar N-acetylneuraminic acid also known as sialic acid aids the immune system.  Without this assistance the immune system would not be strong enough to fight off the fungal conidia.

Sialic acid-dependent recognition of laminin and fibrinogen by Aspergillus fumigatus conidia

JP Bouchara, M Sanchez, A Chevailler, A Marot-Leblond, JC Lissitzky, G Tronchin and D Chabasse
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire, Angers, France.

Abstract:
In an attempt to define the molecular basis of the adherence of Aspergillus fumigatus conidia to the host tissues, a step which might be mediated by the recognition of basement membrane laminin or fibrinogen, we analyzed the binding of these glycoproteins by flow cytometry and a microtiter plate adherence assay. Flow cytometry revealed that the binding of fluorescein isothiocyanate-labeled laminin to conidia was saturable and specific. Moreover, the ability of conidia to bind laminin increased with their maturation. Competition experiments showed a cross-reactivity between laminin and fibrinogen binding and a lack of interactions with glycosaminoglycans. In addition, the binding of laminin was not inhibited by the different adhesive synthetic peptides tested. Furthermore, the microtiter plate assay of adherence to chymotrypsin degradation products of laminin or fibrinogen purified by gel filtration suggested a unique binding site common to sequential degradation fragments or the presence of multiple binding sites on the two ligands. Therefore, the role of carbohydrates in the recognition process was investigated. Among the carbohydrates tested, constitutive of the conidial wall or of the oligosaccharide side chains of laminin and fibrinogen, only N-acetylneuraminic acid and sialyllactose inhibited the binding of these glycoproteins to conidia. In conclusion, these results strengthen the idea that the laminin and fibrinogen receptors in A. fumigatus are identical and suggest an interaction mediated by a sialic acid-specific lectin of the conidial wall.

Infect. Immun., Jul 1997, 2717-2724, Vol 65, No. 7
Copyright © 1997, American Society for Microbiology

http://iai.asm.org/cgi/content/abstract/65/7/2717

« Last Edit: May 27, 2008, 12:12:44 AM by JC Spencer »

Offline JC Spencer

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The sugar that holds life together - a more comprehensive report
« Reply #3 on: May 16, 2008, 10:12:37 PM »
The Sugar Bond for LIFE

This is a more comprehensive report on the sugar that holds life together.  This is a short significant lesson in glycomics and is a key to LIFE.

Healthful sugars hit the NEWS this past week as it was reported that certain sugars hold cells together and can link to treatment for autoimmune diseases.  The University of New Hampshire Glycomics Center reported that their scientists identified a specific carbohydrate structure that confers anti-inflammatory activity to a glycoprotein antibody.  That sugar is sialic acid (N-acetylneuraminic acid) that I mention in my book, Expand Your Mind - Improve Your Brain.

The German scientist Ernst Klenk in 1942 coined the word ganglioside for lipids newly isolated from ganglion cells of the brain.  These oligoglycosylceramides contain N-acetylneuraminic acid (sialic acid) and join, by way of glycosidic linkages, to the monosaccharides.

I discuss the importance of pH in my book and it is very interesting that the polar head groups of the lipids that Ernst Klenk worked with carry a net-negative charge at pH 7.0. This is why they are able to link.  A lower pH would be too acid and push them apart. (over simplification)

In June 1996 I was fascinated with natural plant chemicals.  This was prior to my knowing anything about glycoproteins.  I had not even heard the term glycoprotein.  However, in a publication called phytochemical NEWS, I wrote an article entitled Super Glue Hormones Bond Living Cells Together.  Stabilizing Metabolic Chaos with Eicosanoids.  Eicosanoid is a lipid mediator of inflammation.  The aging process is directly associated to improving hormonal balance with the key factors being the ability to regulate insulin and the eicosanoid hormones.

I will quote here a snippet from that article:

(quote)
Optimal health of body and mind is achieved only when metabolic equilibrium allows peak efficiency.  Hormones shifting out of balance compromise the healthy metabolic state and cells come unglued.  This is called aging or disease.

Specific phytochemicals can play a major role in the balancing act of hormones and the stabilization of living cells.  These hormones are the metabolic regulators to every cell in the body.  So, WHAT CONTROLS THE HORMONES?

Scientist have discovered “trigger point functions” more powerful than the endocrine hormones.  THESE SUPER-HORMONES HOLD THE KEY TO LIFE.  Instructing other hormones, they play the major role of giving orders to every cell of the body.
(unquote)

I may make that whole article available if people request it.
« Last Edit: May 17, 2008, 12:29:16 AM by JC Spencer »

Offline JC Spencer

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Healthful sugars are the glue that pulls things together
« Reply #2 on: May 15, 2008, 09:54:14 AM »
The scientific fact that healthful sugars not only hold things together in the human body, healthful sugars pull things together.  This sugar fact resounded throughout the scientific community this week.  This is the kind of sugar research that will propel glycomics to the forefront of medicine with new sugar drugs and with natural means by the general public simply eating these sugars. The debate will go on that eating healthful sugars will not work.  Results in evidence based nutrition is mounting that indeed neurodegenerative challenges are improving in some people.

It is good for us to remember that over a million people died of scurvy before the lemon was accepted as the treatment and cure for that deadly disease.  Medical science has made astounding advancements in understanding how the human body works.  Add to our vast medical knowledge a little education in nutrition and we can turn around the healthcare system of a country.

"Carbohydrates are the glue that pulls things together, the cell surface matrix in which cells communicate, and they provide the connections for signal transduction. It's only been within the last decade that we've realized that such structures are critical for all kinds of biological function," says Vernon Reinhold, director and research professor at the University of New Hampshire Glycomics Center. "Now that we can define precise structures, we can begin to understand their function. This structure-functional relationship will have a huge impact on our health in respect to immune regulation."
« Last Edit: May 15, 2008, 10:20:41 AM by JC Spencer »

Offline JC Spencer

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How sugars deal with inflammatory activity and autoimmune diseases
« Reply #1 on: May 13, 2008, 08:33:20 PM »
Comments by J. C. Spencer
Research confirms the role glycomics will play in tomorrow’s healthcare.   The science of the sugars that form glycoprotein receptors is growing rapidly.  Glycoproteins cover human cells like fuzz on a peach and is the OS (operating system) for the data of the DNA, RNA, and cell signals.  Nearly 450,000 references to published papers on glycoproteins are available on the NIH (National Institutes of Health) website at www.pubmed.gov .  This press release deals with how these sugars deal with anti-inflammatory activity and improve autoimmune diseases.


Genetic Engineering News (press release) - New Rochelle, NY, USA
DURHAM, NH Researchers at the University of New Hampshire Glycomics Center have helped identify a specific carbohydrate structure.

May 13 2008
Sugar linkage could lead to better treatment for autoimmune diseases

UNH Glycomics Center, Rockefeller University scientists identify linkage

DURHAM, N.H. Researchers at the University of New Hampshire Glycomics Center have helped identify a specific carbohydrate structure that confers anti-inflammatory activity to a glycoprotein antibody that could lead to improved treatment of autoimmune diseases like lupus or rheumatoid arthritis. The study, reported in a recent edition of the journal Science, was led by immunologist Jeffrey Ravetch of Rockefeller University.

The work revolves around immunoglobulin G (IgG), the most abundant antibody in blood plasma. Intravenous immunoglobulin (IVIG) has within it a trace amount of a very active material that is effective in relieving the inflammatory affects of lupus, rheumatoid arthritis, asthma, and other autoimmune disorders. But because of the trace amounts of active material, effective doses of IVIG need to be very high, frequently leading to unwanted side effects.

This study involved rebuilding the human IVIG into a fully active molecule with a slight modification to a carbohydrate residue. These carbohydrate structures are linked to the immunoglobulin and referred to as glycans, and on the tip of this glycan is a specifically linked sialic acid. All the sialic acid on IVIG was converted to the active linkage that confers anti-inflammatory properties.

Understanding and analyzing the exact structure of sialic acid was the contribution of the UNH Glycomics Center, headed by director and research professor Vernon Reinhold. The center has developed tools and protocols using multidimensional mass spectrometry to determine the structure and functional relationships of these carbohydrates. Reinhold notes that while most biopolymers are linear and thus relatively easy to sequence, bush-shaped carbohydrates have proved challenging.

With sequential mass spectrometry, we systematically untangle this bush, says Reinhold. We take it down to the trunk then try to put it back together to determine its structure.

Reinhold and Glycomics Center research scientist David Ashline helped Ravetch pinpoint exactly how sialic acid was linked, which let the researchers engineer a synthetic human antibody that mimicked the linkages in IgG, providing an IVIG with enhanced activity for treatment of autoimmune diseases. In the Science paper, the researchers report that when given to arthritic mice, the engineered IgG was about 30 times more effective than IVIG.

Now that we know what the exact structure is, we can build on it, says Reinhold. Just as once you know what the motor in a car is, you can modify and make it more effective, and in principle, if you know the antigen, you can build the antibody.

Beyond this work with IgG, the Glycomics Center is demystifying the carbohydrate connections in cancer that contributes to metastatic growth and in avian flu where sialic residues on airway surface tissues serve as doorways for viral entry.

Carbohydrates are the glue that pulls things together, the cell surface matrix in which cells communicate, and they provide the connections for signal transduction. Its only been within the last decade that weve realized that such structures are critical for all kinds of biological function, says Reinhold. Now that we can define precise structures, we can begin to understand their function. This structure-functional relationship will have a huge impact on our health in respect to immune regulation.
###
To read the abstract of the article, from the April 18 issue of Science, go to http://www.sciencemag.org/cgi/content/abstract/sci;320/5874/373.

Contact: Beth Potier
beth.potier@unh.edu
603-862-1566
University of New Hampshire
« Last Edit: May 13, 2008, 11:38:30 PM by JC Spencer »