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MONOGRAPH
ON OXIDATIVE STRESS, THE
BODY’S ANTI-OXIDATION CYCLE __________________________________________________________________________________________________________________________________________________________ In humans, oxidative stress is involved in many diseases, such as atherosclerosis, Parkinson's disease, Heart Failure, Myocardial Infarction, Alzheimer's disease and chronic fatigue syndrome, but short-term oxidative stress may also be important in prevention of aging by induction of a process named mitohormesis.[1] Reactive oxygen species can be beneficial, as they are used by the immune system as a way to attack and kill pathogens. Reactive oxygen species are also used in cell signaling. This is dubbed redox signaling. Free radicals are unstable chemicals produced within the cells of the body. These chemicals are electron thief’s, and steal electrons from hundreds of other process chemicals, within the cells of the body. Electrons are the glue that hold atoms together. When electrons are taken away, the victim molecules fall apart, are fragmented, or change shape. All of these detrimental effects cause a cascade of fatal destruction to the cells processes, and ultimately causes unwanted cell proliferation (cancer), cell arrest, or demise of the cell. (1 ) ________________ Within the cells, there are organelles called the mitochondria. They produce energy molecules, through a multiple step process, starting with the break down of glucose. Even, a small, one percent inefficiency of this process, causes the formation of super oxide (O2)-, the first primary free radical thief. This free radical goes on to attack iron sulfur centers in a variety of enzymes. Enzymes are catalysts which cause the normal cell reactions to occur at a reasonable rate. When catalysts are destroyed, downstream reactions, do not occur, and the cell is left with deficiency of chemistry, necessary for efficient cellular functions. Super oxide (O2)-, is degraded to H2O2, hydrogen peroxide, by other protective enzymes in the cell, like SOD,(super oxide dismutase). However, H2O2, hydrogen peroxide, can react with transition metals, to produce the highly reactive hydroxyl free radical (OH)-, a far more damaging molecule to the cell. (2-3 ) __________ In addition to forming H2O2, (O2)-, and (OH)-, the body produces NO, nitric oxide. This free radical gas is used by our body’s immune system to kill aberrant cells, like cancer. The H2O2 and (O2)- rapidly react with NO, nitric oxide, to generate cytotoxic peroxynitrite anions (ONOO)-. Peroxynitrite goes on to react with CO2, carbon dioxide, leading to protein damage via the formation of nitro tyrosine and lipid oxidation. There are greater than a thousand proteins in every cell. The cell membrane is made of lipids. Both the lipids and proteins are in the direct line of fire, of free radicals. (3) _________ This free radical cascade reaction, leads to destruction of the cell structure, to the active chemicals doing cellular work, the proteins which communicate within the cell, as well as the protein catalysts which cause normal cell process to occur. Beyond these processes, RNA within each cell is easily compromised. RNA is the chemical messenger which is transcribed to produce all of the proteins needed within the cell. Oxidation within the cell nucleus, causes DNA mutations, leading to cancer and a host of disease states. (4 ) _____ The cells protect against this cascade of reactive oxygenated free radical chemicals by providing an integrated system, the bodies antioxidant cycle. This cycle quenches and absorbs free radicals. When the body’s anti-oxidant’s cycle capacity, to protect the cell is exceeded, the cell is termed to be in “oxidative stress”. The chemistry of this process is large and complex, to say the least. Biological antioxidants include glutathione, vitamins like E,D,C, B, carotenoids, ascorbic acid, niacin, selenomethioneine, uric acid, lipoic acid, L-ergothioneine, polyphenols, catalase, glutathione peroxidase, antioxidant genes expressing many of these chemicals, amino acids, proteins, protein enzymes like SOD, and long chain lipid ER chemicals. (5-6) _________ The cells ability to protect itself is multifaceted. There is not any “one magic bullet”, nor one simple step used to stop free radical destruction. The cell’s internal and external surfaces have “sensors / receptors”. These sensors are composed of complex sugar molecules, glycol-proteins, lipids, small organic chemicals and proteins. When aberrant behavior is detected, these sensors send signals. Signals, are sent through a cascade reaction of hundreds of proteins, to multiple locations within and outside the cell. One step is to cause the genes within the cell to synthesize proteins, and protein catalysts. Another step is to move metal ions in and out of the cell to change its ph, and create a solubility gradient, making it easier for the cell to defend itself, and hard, for the free radicals to exist. Small organic chemicals are shuttled into or out of the cells. These are molecules that scavenge excess electron density. An example would be vitamin E, selenomethioneine, polyphenols, small carboxylic acids like lipoic acid, vitamin B12, Vitamin C, uric acid. Then, there is a specific cycle which uses ergothioneine, in concert with vitamin C, to shunt electrons, in the myoglobin oxidative cycle. Ergothioneine has many functions and is so valuable to the body that it has its own transport system. This system allows ergothioneine to be transported through the body to areas of high oxidative stress. These areas would include the liver, kidneys, heart, and eyes. (7) _________ All of this process has as many as twenty intermediate steps. Each step requiring separate molecules to make it all work. The body’s cells needs a complete long list of small chemicals, proteins, catalysts, transition metals, vitamins, and anions. And, these chemicals need to be provided in the right ratios. This list of chemistry comes from the food we eat. This matrix of chemistry, received on a daily basis is necessary for on going cellular defense. Taking a supplement of one component of this process may or may not be helpful. What is important, is a complete balance of the right chemistry received at the cellular level on a daily basis. __________________________________________________________________________________________________________________________________________ WHAT IS IN MUSHROOMS ________ The mushrooms are a class of fungi which possesses a wide variety of functional chemistry. Fungi live via an extra cellular life process. The mushrooms exude protein catalysts which digest the foods around it. The digestion is then transported back into the fungal cell for use. Because of this feeding method, mushrooms posses a large amount of Enzymes.(8-12) ___________ The mushroom's cellular structure is composed of hundreds of very specific types of complex sugars, called beta-glucans. Along with these long chain sugars, the mushrooms also produce glycol-proteins. Sugar structures attached to a protein stem. Enzymes, beta glucans and glycol-proteins all have very specific shapes which interact with structures that are on the cells membrane. These “sensors / receptors” on the inside and outside of the cells couple with the mushrooms chemistry and cause the body’s cell to produce a multitude of proteins. Each protein reacting with the next, like a relay race with many runners involved. This is a cascade reaction. These cascade reactions can be used by the cell to communicate within the cell, or between cells in the body. They can cause genes within the DNA to create more proteins for different biological activity, or cause more enzymes to be produced, which assists many more chemicals to be formed. (9-23) ___________ Cell transductance (communication through these sensors / receptors), can open the cell walls to a flood of calcium ions, or increase the flow of glucose, adrenaline, and insulin across the membrane. These sensors can cause the synthesis of good cholesterol versus bad cholesterol, can cause chemicals to dilate blood vessels, and cause the creation of NO, nitric oxide, to kill cancer cells, as well as produce chemicals to quench free radicals. Because medicinal mushrooms have their own life to live, which in many respects is very similar to an animal’s cell life. Remember, fungi breathe oxygen and exhale carbon dioxide, just as humans do; the mushroom cell needs and uses the same basic building blocks. Fungi therefore contains all the essential amino acids, nucleotides, transition metals, vitamins, including B12, C, niacin, D, L-ergothioneine and a large contingent of enzymes to make the process work. The components of Mushroom blends, are the very same that our cells need. The scientist can create blends according to the health challenges for consumption. These certain mushroom blends are not a neutraceutical mix of chemicals put together in a lab. It is an ancient living life form, and has the correct ratio and amounts of two to four thousand biological chemicals. Specific mushroom blends have evolved along side animals, and man is consuming this whole food, reaping the benefit of chemistry that was explicitly designed for a complete healthful life. (24-33) ______________________________________________________________________________________________________________________________________________________________________________________________________________ BIBLIOGRAPHY ________________________________________________________________________________________________________________ 1) Dastrun et al. (2004), Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells, Dept. cell biology, Institute of Biomembranes, Utrecht University, The Netherlands, Online Pub. 2) Kakkura B., (2006), Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle, Dept of Obstetrics and Gynecology, University of Siena, Italy, Online Pub 3) Jeffery Klein, (2003), Susan Ackerman, Oxidative stress, cell cycle, and neurodegeneration, J. Clin Invest, 111;785-793 4) Nagy Z, Esiri, M (1998), The cell division cycle and the pathophysiology of Alzheimer’s disease. 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Transporter Department of Pharmachology, University of Cologne, Germany 8) Kutner& Jablonska, (2000), Vitamin D deficiency associated with cancers, Grant 2002: Hansen & Hamberg, 2001: Online Pub 9) Billaudel B, Barakat, L. (1998) Vitamin D3 deficiency and alterations of glucose metabolism in rat endocrine pancreas, Diabetes Metabolism 24, 344-350 10) S.P. Wasser, Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides (2002), Applied Microbial Biotechnology 60, pp258-274 11) Borchers AT, Stern JS, Hackman RM (1999) Mushrooms, tumors and immunity, Soc. Exp Biol Med 221; pp 281-293 12) Fullerton SA, Samadi AA, (2000), Induction of apoptosis in human prostatic cancer cells with beta-glucan from Maitake, Mol Urol 4: pp7-13 13) Breene W., Nutritional and Medicinal Calue of Specialty Mushrooms (1989), J. of food protection vol 53: No. 10, pp 883-894 14) Nathon Sharon, Halina Lis (1993), Carbohydrates in Cell Recognition, , Scientific America, Jan 1993 15) So-Young Won and Eun-Hee Park (2005), Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris, , College of Pharmacy, Sookmyung Women’s Unicersity, Seoul 140-742, South Korea, Journal of Ethnopharmacology, Vol 96, issue 3, 15 Jan 2005 p 555-561 16) Chiou et al, 2000, Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis, Life Sciences 66 (2000), pp 1369-1376 17) Ingber et al, 1990 D. Ingber, T. Fujita, Synthetic analogs of fumagillin that inhibit angiogenesis and suppress tumor growth, Nature 348 (1990), pp 555-557 18) Koh et al, 2003 J.H. Koh, K.M. Kim, Ant fatigue and anti stress effects of the hot water fraction from mycelia of Cordyceps sinesis, Biological and Pharmaceuetin 26 (2003), pp 691-694 19) Bok et al, 1999 J.W. Bok, L. Lermer, J. Chilton, H.G. Klingerman, Antitumor sterols from the mycelia of Cordyceps sinensis, Phytochemistry 51 (1999), pp 891-898. 20) Bourlon, P. M., Billaudel, B& Faure-Dussert, A. (1999), Influence of vitamin D3 deficiency and 1, 25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas, Journal of Endocrinology, 160, 87-95 21) Ohno, R., Imai, K. Yokomaku, S. & Yamada, K. (1975) Antitumor effect of protein bound polysaccharide preparation, PSK against 3-methylcholanthrene induced fibrosarcoma in C57BL/6 mice. Gann 66 697-681 22) Matsunaga, K., Oguchi, Y, Ando T, (1980) Effect of PSK on intestinal immune system in tumor bearing mice. Proceedings of the Japanese Cancer Association, 29th Annual meeting, p145 23) Muto, S. Kobayashi, A. (1982) Structure and antitumor effect of PSK (Kreston): mechanistic aspects of the antitumor activity. Proceedings of 2ndInternational Conference of Immunopharmachology, p 308 24) Muto, S., Kobayashi, A. (1983) Structural analysis and antitumor effect of PSK, Proceedings of 13th International Congress of Chemotherapy, Vienna: part 287, pp 37-40 25) Morimasa, K. Yamana, S. Matsueda, H. (1980) Immunostimulent therapy with protein bound polysaccharide preparation in patients with SLE or RA. Clinical Immunology 12: 393-398 26) Aoki T (1984) Fenichei RL, Chirgis MA, Immune modulating agents and their mechanisms, Immunol Stud 25, 62-77 27) Fujimiya Y, Yamamoto H, Noji M (2000) Peroral effect on tumor progression of soluable B-1,6 glucans prepared by acid treatment from Agaricus blazei, Agaricaceae Higher Basidiomycetes, Int. J Med Mushrooms 2: pp43-49 28) Che Ys, Lin Lz, Clinical observation of therapeutic effects of JinShuBao on coronary heart disease, hyperlipidemia, and blood rheology. Chinese traditional herbal drugs 1996;27 (9) pp 552-553 29) Kiho T, Yamane A, Polysaccharides in fungi. XXXVI. Hypoglycemic activity of a polysaccharide (CS-F30) from the cultured mycelia of Cordyceps sinensis and its effect on glucose metabolism in mouse liver. Biol Pharm Bull (1996);; 19(2) p294-296 30) Shao G. You Zj, Treatment of hyperlipidemia with Cordyceps sinensis; a double blind placebo control trial. Int j oriental Med 1990;15(2);77-80 31) Mizuno T. et al Antitumor active polysaccharides isolated from the fruiting body of Hericium erinaceum, an edible and medicinal mushroom called yamabushitake Biosci, Biotech, Biochem 56 (2), 347-348 (1992) 32)S. Konno, H Tazaki et al, A possible hypoglycemic effect of Maitake mushroom on type 2 diabetic patients, Diabetic Medicine, Vol 18 Issue 12 p 1010 Issue 12 Dec 2001 33) Kaoru Nagai, Akiko Chiba et al, Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress dependent Neuro2a cel
Fungi such as mushrooms
and yeast also have cell walls, but these are made of chitin. Chitin is a polysaccharide; it is synthesized from units of N-acetylglucosamine(more completely, N-acetyl-D-glucos-2-amine). These units form
covalent β-1,4 linkages (similar to the linkages between glucose units forming cellulose). Chitin may therefore be described as cellulose with one hydroxyl group on each monomer substituted with an acetylamine group. This allows for increased hydrogen bonding between adjacent polymers, giving the chitin-polymer matrix increased strength. Chitin is one of many naturally occurring polymers. Its breakdown may be catalyzed by enzymes called chitinases, secreted by microorganisms such as bacteria and fungi, and produced by some plants. Some of these microorganisms have receptors to simple sugars from the decomposition of chitin. If chitin is detected, they then produce enzymes to digest it by cleaving the glycosidic bonds in order to convert it to simple sugars and ammonia. Chemically, chitin is closely related to chitosan (a more water-soluble derivative of chitin). It is also closely related to cellulose in that it is a long unbranched chain of glucose derivatives. Both materials contribute structure and strength, protecting the organism. Vitamin D Deficiency: The New England Journal Of Medicine: http://www.vitamindhealth.org/OLD/images/stories/articles/holicknejm2007.pdf Nutritional: The Journal of Agricultural and Food Chemistry: |
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