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- Kulseth, Mari Ann, et al.
(författare)
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Serglycin expression during differentiation of U937-1 cells
- 1998
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Ingår i: Glycobiology. - 0959-6658 .- 1460-2423. ; 8:8, s. 747-753
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Tidskriftsartikel (refereegranskat)abstract
- Serglycin is the major proteoglycan in most hematopoietic cells, including monocytes and macrophages. The monoblastic cell line U937-1 was used to study the expression of serglycin during proliferation and differentiation. In unstimulated proliferating U937-1 cells serglycin mRNA is nonconstitutively expressed. The level of serglycin mRNA was found to correlate with the synthesis of chondroitin sulfate proteoglycan (CSPG). The U937-1 cells were induced to differentiate into different types of macrophage-like cells by exposing the cells to PMA, RA, or VitD3. These inducers of differentiation affected the expression of serglycin mRNA in three different ways. The initial upregulation seen in the normally proliferating cells was not observed in PMA treated cells. In contrast, RA increased the initial upregulation, giving a reproducible six times increase in serglycin mRNA level from 4 to 24 h of incubation, compared to a four times increase in the control cells. VitD3 had no effect on the expression of serglycin mRNA. The incorporation of (35S)sulfate into CSPG decreased approximately 50% in all three differentiated cell types. Further, the (35S)CSPGs expressed were of larger size in PMA treated cells than controls, but smaller after RA treatment. This was due to the expression of CSPGs, with CS-chains of 25 and 5 kDa in PMA and RA treated cells, respectively, compared to 11 kDa in the controls. VitD3 had no significant effect on the size of CSPG produced. PMA treated cells secreted 75% of the (35S)PGs expressed, but the major portion was retained in cells treated with VitD3 or RA. The differences seen in serglycin mRNA levels, the macromolecular properties of serglycin and in the PG secretion patterns, suggest that serglycin may have different functions in different types of macrophages.
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- Westling, Camilla, 1973-
(författare)
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N-Unsubstituted Glucosamine Residues in Heparan Sulfate and Their Potential Relation to Alzheimer's Disease
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heparan sulfate (HS) is a linear polysaccharide, located on the surface and in the extracellular matrix of most cells, that regulates functions of numerous proteins. HS-protein interaction is mainly mediated by sulfate groups found in N-sulfated (NS) regions of the HS, but may also involve rare HS substituents such as N-unsubstituted glucosamine (GlcNH2) residues. The location of GlcNH2 in an HS-epitope recognized by the monoclonal antibody 10E4, that specifically stains the prion lesions in scrapie-infected murine brain, suggests an involvement of GlcNH2 in prion disease and other amyloid-related disorders. HS in general is strongly associated with amyloidosis, including Alzheimer’s disease (AD). Therefore, the aims of this thesis were to structurally characterize GlcNH2-containing HS sequences found in native tissues, to further study HS epitopes recognized by 10E4, and to investigate the possible role(s) of GlcNH2 and other HS structures in binding to amyloid β peptide (Aβ) (core material in AD plaque lesions, also stained by 10E4).The GlcNH2 content (0.7-4% of total disaccharide units) varied between HS from different tissues. Most GlcNH2 units were found in poorly modified N-acetylated (NA-) or NA/NS-domains, located toward the polysaccharide-protein linkage region.Binding of human cerebral cortex HS to Aβ(1–40) monomers requires N-, 2- and 6-O-sulfation of HS, while binding to Aβ fibrils requires N- and 2-O-sulfation only. GlcNH2 units do not appreciably contribute to interaction with Aβ. Aβ fibril-binding HS domains also bind to fibroblast growth factor 2 (FGF-2), indicating that Aβ (neurotoxic) and FGF-2 (neuroprotective) may compete for common binding sites in HS. However, Aβ had no effect on FGF-2-induced MAPK signaling in NIH 3T3 fibroblasts.Continued studies on 10E4-antigenic HS epitope(s) showed that binding of 10E4 to the previously identified antigenic tetrasaccharide, ∆UA-GlcNH2-GlcA-GlcNAc, requires the nonreducing hexuronic acid (∆UA) to be 4,5 unsaturated (induced by lyase cleavage), and thus is artificial. Further studies are needed to clarify the potential involvement of GlcNH2 in 10E4-recognition of the native HS epitope(s).
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