(From the July 2014 newsletter)
We know that genetic information is carried by our genes in DNA, and by the RNA and proteins resulting from the DNA-carried information. But glycans also carry information in processes like cell growth and apoptosis, folding and routing of glycoproteins, cell-cell interactions and cell adhesion and migration.
Lectins are proteins that recognize specific glycan configurations and are involved in recognition of pathogens. The carbohydrate-binding activity of most lectins resides in a small portion of the protein. For a history of 130 years of research on lectins, see the review by Nathan Sharon and Halina Lis (2004)
People old enough to remember the Cold War may remember a particularly nasty example of lectin use in a political assassination: ricin. How does ricin kill? It binds to human cells containing either terminal N-acetyl galactosamine or beta-1,4-linked galactose residues. Another example of a very relevant lectin is the influenza virus hemagglutinin, responsible for the attachment of the virus to the host cells, a prerequisite for infection.
At Skin Actives, we have been using Glycobiology research for quite a while, and have written in our newsletter about the benefits of yeast beta glucan. Dectin-1 is a lectin, a small trans-membrane receptor which recognizes beta-1,3 and beta-1,6-glucans, granting humans innate immunity.
Lectins and the Skin
The first human lectin was identified in 1974, but the work on skin lectin receptors lags well behind that on receptors present in other human organs. There is a receptor lectin in fibroblasts and keratinocytes that recognizes rhamnose (a methyl pentose) not synthesized by humans. From the point of view of skin aging, an issue so dear to the skin care industry (including us at SAS!) it is known that applying rhamnose containing glycans to the skin stimulates cell proliferation, decreases elastase-type activity, stimulates collagen biosynthesis, and protects hyaluronan against free radical mediated degradation. This is a very useful effect, even if we don’t know what the primary function of this receptor lectin is supposed to be. Based on what we know about lectin receptors, we can hypothesize that they have something to do with the beneficial bacteria that live on our skin, but the receptor could also be just an evolutionary leftover. Living organisms, even viruses, possess sophisticated enzymatic systems devoted to making the glycans and also the lectins to recognize them, so I am sure there are more interesting stories to be discovered by scientists that will be later used in medicine and even skin care.
People with skin conditions characterized by excessive cell division, like psoriasis, should avoid glycans that promote cell division (dectin-1 seems to be over-expressed in psoriatic skin), but glycans that modulate the immune response, like fucoidans and yeast beta glucans, should be fine.
Lectins may have implications for allergy: galectin-3 is highly expressed in epithelial cells including keratinocytes and is involved in the pathogenesis of inflammatory skin diseases by affecting the functions of immune cells. For example, galectin-3 can contribute to atopic dermatitis and may also be involved in the development of contact hypersensitivity by regulating migration of antigen presenting cells. Human milk contains non-digestible oligosaccharides, another connection to the role of glycans in allergy.
Among the cell-cell recognition related lectins, there is one receptor involved in the uptake of melanosomes by keratinocytes, but we are a long way from being able to use this information for a therapy in melasma and hyperpigmentation.
Glycan vs. Polysaccharides (see also Newsletter September 2012 and polysaccharide refresher)
The terms glycan and polysaccharide were originally synonyms meaning “compounds consisting of a large number of monosaccharides linked glycosidically”. Nowadays the term glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan, even if the carbohydrate is only an oligosaccharide.
Glycans usually consist only of monosaccharides linked by O-glycosidic linkages. For example, cellulose is a glycan (or, to be more specific, a glucan, because it is made of glucose) composed of β-1,4-linked D-glucose. Chitin is a glycan composed of β-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo- or heteropolymers of monosaccharide residues, linear or branched.
Glycans at Skin Actives Scientific
We use many glycans in our products: hyaluronic acid, pullulan, Aloe barbadensis. pectin polysaccharides (rich in uronic acid), apple pectin, galactoarabinan, oat beta-glucan, Laminaria Japonica fucoidan, oat beta glucan, Opuntia (prickly pear) glucan.
Our Glycan-7 booster blend is a combination of plant and fungal extracts that will promote collagen synthesis and fibroblast division and modulate the immune response. This mix includes glycans from aloe, apple, larch, yeast, oat, and brown algae. This group of seven is just a selection from the many glycans we offer that benefit the skin.
Aloe Vera – The gel obtained from Aloe barbadensis plant improves skin hydration, has anti-inflammatory properties and aids healing of cuts, grazes, burns and insect bites. The polysaccharides in this extract include acetylated mannans.
Apple pectin is a complex polysaccharide that contains rhamnose. Fibroblasts contain receptors for rhamnose (more about this later), and binding of rhamnose to the receptor leads to increased synthesis of collagen and strengthened epidermal-dermal junction. Apple pectin helps thicken skin thinned by aging.
Larch arabinogalactans – In native North American Indian tribes, larch was used as a poultice on sores, ulcers, burns and to alleviate itching. When biochemists looked into larch, they found that arabinogalactans stimulate dermal fibroblast activity and proliferation, and promote keratinocyte differentiation and the production of keratinocyte growth factor. Note: Dr. Andrew Weil, a proponent of integrative medicine (which incorporates scientifically proven botanicals into the daily practice of medicine) uses this active in his Origins line.
Yeast beta glucan – The cell wall of yeast is very complex, with a structure that includes beta(1–> 3)-glucan, beta(1–> 6)-glucan, chitin, and mannoprotein. When we come in contact with these special glycans, our immune system is activated so that, when a pathogen is encountered, we are better able to deal with it and stop an infection. Apparently, this response may also prepare us to stop our own “gone bad” cells, those that have lost the capacity to control cell division and have become cancer cells. A great advantage to allergy sufferers: yeast beta glucan (and that of other fungi) seems to decrease the tendency to allergic response and inflammation, and as an added bonus it tightens your skin. A recently discovered lectin is dectin-1, a small cell surface protein that recognizes beta 1,3 and beta1,6-glucans and is a source of innate immunity, i.e. immunity that does not require previous exposure to pathogen.
Fucoidans are sulfated polysaccharides that when applied to the skin increase the density of collagen bundles, decrease activity of proteases (enzymes that break down dermal proteins), increase scavenging of free radicals, and increase cell proliferation. In addition to helping with healing and collagen synthesis, fucoidan inhibits the replication of many viruses, including herpes, human cytomegalovirus, and HIV-1.
Prickly pear (Opuntia fruit) extract – This beautiful fruit contains methylated rhamnogalacturonans (L-arabinose and D-xylose are also represented), giving this extract medicinal powers in treatment of burns, edema, and asthma.
Oat beta glucan – Cereal beta-glucan is a mix of linked (1 -> 3) (1 -> 4)-beta-D-glucan with anti-inflammatory properties.
Sharon, N. and Lis H. (2004) History of lectins: from hemagglutinins to biological recognition molecules, in Glycobiology, 14: 53R–62R.
Faury G, Ruszova E, Molinari J, Mariko B, Raveaud S, Velebny V, Robert L. (2008) The alpha-1-rhamnose recognizing lectin site of human dermal fibrolasts functions as a signal transducer. Modulation of Ca++ fluxes and gene expression. Biochim.Biophys.Acta. 2008. pp. 1388-1394.
Noss, I; Doekes, G; Thorne, PS; Heederik, DJJ; Wouters, IM (2013) Comparison of the potency of a variety of beta-glucans to induce cytokine production in human whole blood Innate Immunity 19: 10-19.
Oh JH, Kim YK, Jung JY, Shin JE, Chung JH. (2011) Changes in glycosaminoglycans and related proteoglycans in intrinsically aged human skin in vivo. Experimental Dermatology. 20:454-6
Larsen, Larissa, Chen, Huan-Yuan; Saegusa, Jun, Liu, Fu-Tong (2011) Galectin-3 and the skin. J Dermatological Science, 64: 85-91.