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RADIATION TOXICOLOGY.
GLYCOPROTEINS.
DMITRI POPOV MD (RUSSIA), PHD RADIOBIOLOGY.
ADVANCED MEDICAL TECHNOLOGY AND SYSTEMS INC. CANADA.
GLYCOPROTEINS
Research Proposal:
Radiation Protection: Radiation Toxicology. Glycoproteins. Pathway to
biodozimetry and pathway to cancer diagnosis.
Dmitri Popov
Full-text available Research Proposal Aug 2015
Add resources
File name:Radiation Toxicology Glycoproteins.pptx
DOI:10.13140/RG.2.2.13696.64001
GLYCOPROTEINS
Keywords:
ACUTE RADIATION SYNDROMES, BIOLOGICAL RRADIATION
EFFECTS, GAMMA RADIATION, RADIOSENSETIVITY,
BIOLOGICAL EFFECTS.
GLYCOPROTEINS
Glycoproteins play key roles in inflammatory and pathological
processes. The Differential Diagnosis of Acute Radiation Syndromes
can be assessed by quantifying circulating levels of glycoproteins
with ELISA.
GLYCOPROTEINS
Inflammatory glycoproteins are predominantly synthesized
and secreted by hepatocytes but can be produced by
activated macrophages and neutrophils in the periphery.
GLYCOPROTEINS
E. Gruys, M.J. Toussaint, T.A. Niewold, S.J. Koopmans, Acute phase
reaction and acute phase proteins, J. Zhejiang Univ. Sci. B 6 (11)
(2005) 10451056.
GLYCOPROTEINS
Acute-phase proteinsare a class ofproteinswhoseplasma
concentrations increase (positive acute-phase proteins) or
decrease (negative acute-phase proteins) in response to
inflammation.
GLYCOPROTEINS
In response to injury, localinflammatorycells (neutrophil
granulocytes,andmacrophages) secrete a number ofcytokinesinto the
bloodstream, most notable of which are theinterleukinsIL1,IL6andIL8,
andTNF. Theliverresponds by producing a large number ofacutephase reactants. At the same time, the production of a number of
other proteins is reduced; these are, therefore, referred to as "negative"
acute-phase reactants. Increased acute phase proteins from the liver
may also contribute to the promotion ofsepsis, or acute radiation
syndromes (after irradiation).
GLYCOPROTEINS
Therefore, there are both intracellular and extracellular post-translational
processes that contribute to the overall diversity of glycan structures
that can occur in any one individual. These are also many factors that
can influence glycan complexity including: 1) cell-type specific expression
of glycosyltransferases, glycosidases, 2) availability of the various
monosaccharides, 3) age, 4) gender, 5) epigenetic background, 5) environment
(e.g. health, diet, smoking and alcohol consumption) and 6)
disease processes (e.g. autoimmune diseases, cancer as well as low grade
inflammatory diseases such as CVD and T2DM).
GLYCOPROTEINS
W. Dijk, G. Turner, A. Mackiewicz, Changes in glycosylation of
acute-phase proteins
(1994) 514.
GLYCOPROTEINS
F. Ceciliani, V. Pocacqua, The acute phase protein alpha1-acid
glycoprotein: a model for altered glycosylation during
diseases, Curr. Protein Pept. Sci. 8 (1) (2007) 91108.
GLYCOPROTEINS.
Besides changes in circulating protein levels, the glycan
structures of acute phase glycoproteins are dynamically
altered by glycosidases, glycosyltransferases and sialyl
transferases in the blood and lymph- circulation.
GLYCOPROTEINS
Glycoproteinsareproteinsthat
containoligosaccharidechains (glycans)covalentlyattached
topolypeptideside-chains.
The carbohydrate is
attached to the protein in aco-translationalorposttranslational modification.
This process is known
asglycosylation.
Secreted
extracellular proteinsare often glycosylated.
GLYCOPROTEINS
Glycoproteins are also often importantintegral membrane proteins,
where they play a role in cellcell interactions. It is important to
distinguish endoplasmic reticulum-based glycosylation of the
secretory system without of reversible cytosolic/nuclear glycosylation.
Glycoprotein of thecytosoland nucleus can be modified through the
reversible addition of a single GlcNAc residues that is consider
reciprocal to phosphorylation and the functions of these are likely to
be additional regulatory mechanism that controls phosphorylationbased signalling
GLYCOPROTEINS
One example of glycoproteins found in the body ismucins, which are secreted in the
mucus of the respiratory and digestive tracts. The sugars when attached to mucins
give them considerable water-holding capacity and also make them resistant
toproteolysis by digestive enzymes.
GLYCOPROTEINS
Sialyl LewisX, also known assialyl LeXandSLeX, is a tetra
saccharidecarbohydratethat is usually attached to Oglycanson the surface of cells. It is known to play a vital role
in cell-to-cell recognition processes.
GLYCOPROTEINS
Sialyl LewisXis also one of the most important blood group antigens
and is displayed on the terminus of glycolipids that are present on the
cell surface. TheSialyl LewisXdeterminant, E-selectinligand
carbohydrate structure, is constitutively expressed on
granulocytesandmonocytesand mediates inflammatory
extravasation of these cells. Resting T and Blymphocyteslack its
expression and are induced to strongly expresssialyl LewisXupon
activation. TheSialyl LewisXdeterminant is expressed preferentially
on activatedTh1 cellsbut not on Th2 cells.
GLYCOPROTEINS
Defective synthesis of the sialyl LewisXantigen results in immunodeficiency (leukocyte adhesion
deficiencytype 2). Defective synthesis can be caused by the loss of fucosyltransferase, impairing the
glycosylation of the glycosphingolipid.
Sialyl Lewis x is being used in studies to fight tumors and cancer cell growth. It has been shown that
there is frequent overexpression of sialyl Lewis x on cancer cells and is found on both N-glycan and Oglycans. Sialyl Lewis x is being researched with CD markers to find new ways to create biosensors for
cancer cells. Also, it is being used in new ways to target cancer cells specifically for cancer treatment.
It plays a key role in the inflammatory response and may be used to increase the leukocyte response to
infections.
Sialyl Lewis x is also being researched for detection and treatment of immune disorders because of its
presence on leukocytes. There is congenital disorder where there is an inclination to recurring severe
infections. This stems from an absence of sialyl Lewis x attached to E-selectin ligands on their
neutrophils. https://en.wikipedia.org/wiki/Sialyl-Lewis_X
GLYCOPROTEINS
Leukocyte homing and cancer metastasis
Sialyl-Lewisxisimportantinleukocytetetheringandrolling.Leukocytesmovethroughthebloodstreamand
thentetherthemselvestotheendothelialwallandrollalongtheendothelialtissuetodetermineiftheywant
toleavethebloodstreamtogettonecessarytissue.
Sialyl-Lewisxisanecessarypartnerforthethreeselectinsthatbindtheleukocyteandendothelialcells.
Whensialyl-LewisxispartofanO-glycanandattachedtoCD34itcanthenbindtoL-selectin.Forthebinding
toL-selectintooccursialyl-Lewis xmustundergosulfation.
Forsialyl-LewisxtoattachtoP-selectinitmustbindtoP-SelectinGlycoproteinLigand-1(PSGL-1)firstwhich
isthensulfatedallowingsialyl-Lewis xtoattachtoP-selectin.Forsialyl-Lewis xtobindtoE-selectinitneedsto
bepartofanN-glycanandthenbindtoCD44orpossiblyglycolipidswhichhavealsobeenimplicatedto
assistinbinding.
Thisbindingallowstheleukocytestosticktoandbereleasedfromtheendothelialcellsasneededtoreach
theirdestination.
Sialyl-Lewisxalsoplaysacriticalroleincancermetastasis,facilitatingtheextravasationofcancercellsoutof
thebloodstreamwhiletheyaremovingthroughthebody.
https://en.wikipedia.org/wiki/Sialyl-Lewis_X
GLYCOPROTEINS
H antigen of the ABO blood compatibility antigens. Other
examples of glycoproteins include:
GLYCOPROTEINS
Most, if not all, external proteins of mammalian cells are
glycoproteins.
These comprise both various receptors and antigenic
determinants.
GLYCOPROTEINS
Thehuman leukocyte antigen(HLA) system is agene
complexencoding themajor histocompatibility complex(MHC)
proteins in humans. Thesecell-surface proteinsare responsible
for the regulation of theimmune system in humans. The HLA
gene complex resides on a 3Mbpstretch withinchromosome
6p 21. HLA genes are highlypolymorphic, which means that
they have many different alleles, allowing them to fine-tune
theadaptive immune system. The proteins encoded by certain
genes are also known asantigens, as a result of theirhistoric
discoveryas factors in organ transplants.
GLYCOPROTEINS.
Inflammatory glycoproteins in cardio-metabolic disorders, autoimmune diseases
and cancer.
Margery A. Connelly a, Eke G. Gruppen b,c, James D. Otvos a, Robin P.F. Dullaart
b,
GLYCOPROTEINS
Knowledge of the membrane glycoprotein patterns on the
surface of normal leukocytes and encoded with the human
leukocyte antigen(HLA) system, and membrane
glycoprotein patterns on surface classes of themajor
histocompatibility complex(MHC) for other vertebrates is
fundamental for the discovery of possible molecular defects
and development of toxic effects associated with Acute
Radiation Syndromes.
GLYCOPROTEINS
Currently, concentrations of individual inflammatory glycoproteins
are determined using immunochemical methods such as enzyme linked
Immuno-sorbent assays (ELISAs), electro-chemiluminescence immuno assay
(ECLIA), luminex based assays, radioimmunoassays (RIA)
and nephelometric assays that quantify the amount of protein present
in biological samples.
Method of Differential Diagnosis of Acute Radiation Diseases was elaborated in All
Union Institute of vet. Medicine. Kazan. Tatarstan. 1990 yy. Authors: Popov D.N.,
Kirshin V.A.
GLYCOPROTEINS.
1. Glycoproteins playing important role in the development
clinical picture and biological sequela after different types of
radiation.