Defects in Proteoglycan Biosynthesis ..

mutants were originally isolated on the basis of resistance to fluoride () but turned out to have a short defecation interval. is a degenerin/epithelial sodium channel type of protein, expressed only in the intestine and possibly concentrated at apical membranes (). The gene encodes an apparently membrane-associated kinase that is expressed in the intestine (+ pharynx and several neurons) beginning from the comma stage; only intestinal expression is necessary for mutant rescue. GFP translational fusions to appear localized to the enterocyte membranes, especially the lateral membranes (). Proteins binding to the protein in a yeast two-hybrid assay have also been identified in the intestine (and other tissues; ). All of the above genes are candidates for participating in signals that originate from the oscillating calcium levels in the posterior intestine and that result in contraction of the posterior body wall muscles (the pBoc phase of defecation). Cycle times are influenced by additional intestinally-expressed genes, for example, genes that influence fatty acid composition ().


Discrete electron dense regions can be detected just beneath the apical, lumenal surface of the intestinal cells, joining each cell to its neighbour (). The nomenclature of these structures has changed over the years but they are now generally referred to as “apical junctions”. The apical junctions are regarded as the counterpart of the bipartite cell junctions seen in epithelia (zonula adherens and septate junctions) and the tripartite structures seen in vertebrate epithelia (tight junctions, zonula adherens and desmosomes). Indeed, many of the proteins found in fly and vertebrate cell junctions have clear homologs in and this is how many of the components were identified. However, the function of each component and its position in the assembly pathway in epithelia can differ markedly from other systems. As particular examples, depletion of cadherins, catenins and proteins such as crumbs () has disasterous consequences for fly epithelia but relatively minor consequences in the intestine (; ). One particular view of the relative positioning of proteins and protein complexes within the apical junctions, is shown in . The WormBook chapter by Labouesse (see ) provides a much more detailed discussion of the important topic of apical-basal polarity in epithelia, including the intestine.

Virus de la hepatitis C y fibrosis - SciELO España

Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

The same defect enhancement has been observed in other disorders of proteoglycan metabolism, namely, the DTDST family of disorders and CHST3 disorders resulting in generalized undersulfation and a lack of 6-O-sulfation of the GAG chains, respectively. Indeed, the sulfation defect was enhanced when fibroblasts were incubated with xyloside suggesting that this condition might mimic the cartilage situation because it is thought that chondrocytes synthesize higher amounts of proteoglycans than any other tissue.


AB - Chondrocytes in arthritic cartilage respond poorly to insulin-like growth factor I (IGF-I). Studies with inducible nitric oxide synthase (iNOS) knockout mice suggest that NO is responsible for part of the cartilage insensitivity to IGF-I. These studies characterize the relationship between NO and chondrocyte responses to IGF-I in vitro, and define a mechanism by which NO decreases IGF-I stimulation of chondrocyte proteoglycan synthesis. Lapine cartilage slices, chondrocytes, and cartilage from osteoarthritic (OA) human knees were exposed to NO from the donors S-nitroso-N-acetylpenicillamine (SNAP) or (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate] (DETA NONOate), by transduction with adenoviral transfer of iNOS (Ad-iNOS), or by activation with interleukin-1 (IL-1). NO synthesis was estimated from medium nitrite, and proteoglycan synthesis was measured as incorporation of 35SO4. IGF-I receptor phosphorylation was evaluated with Western analysis. SNAP, DETA NONOate, endogenously synthesized NO in Ad-iNOS-transduced cells, or IL-1 activation decreased IGF-I-stimulated proteoglycan synthesis in cartilage and monolayer cultures of chondrocytes. OA cartilage responded poorly to IGF-I; however, the response to IGF-I was restored by culture with N(G)-monomethyl-L-arginine (L-NMA). IGF-I receptor phosphotyrosine was diminished in chondrocytes exposed to NO. These studies show that NO is responsible for part of arthritic cartilage/chondrocyte insensitivity to anabolic actions of IGF-I; inhibition of receptor autophosphorylation is potentially responsible for this effect.

Osteoarthritis - Flinders University

...entration of heparan sulfate by enzymatic digestion also reduces HSV infection, which suggests that heparan sulfate, or a molecule with which heparan sulfate associates, plays a role in HSV infection =-=(63)-=-. Furthermore, animal cell mutants with defects in GAG synthesis show either complete (54) or partial (24) resistance to HSV infection, and cells selected for HSV resistance have been shown in some in...