HSPGs

Heparin sulfate proteoglycans (HSPGs) are heavily glycosylated proteins that are part of the extracellular matrix. Interaction with HSPGs help to stabilize and localize extracellular Wnts. 

The syndecan family of heparin sulfate proteoglycans (HSPGs) plays critical roles in several signal transduction pathways, and syndecan 3 intramembrane proteolysis is presenilin/y-secretase dependent (357). COX2 and COXl potentiate ABP formation through mechanisms that involve y-secretase activity. Sulindac sulfide and other NSAIDs (ibuprofen, indomethacin, R-flurbiprofen) selectively decrease the secretion of ABP independently of COX activity, probably via y-secretase inhibition (358-360). Pepstatin A methylester, sulfonamides, and benzodiazepines can also act as potent, noncompetitive, y-secretase inhibitors (335). These are but a few examples of the potential repercussions and biochemical consequences that the pharmacological manipulation of secretases in AD may bring about. 

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

AAV2 and its helper viruses like HSV, AAY2 interacts with the cell surface via heparin sulfate, and AAV internalization is mediated by aV/ 5 integrin, which is also required by adenovirus for uptake. Serotypes other than AAV2 exhibit different tropisms and interact with different cell surface molecules. Some of the cell surface receptors have been identified for AAV3 (HSPG Rabinowitz et al.,... 

Already in 1965, Ryser and Hancock provided evidence that histones and polyamino acids could greatly enhance albumin uptake by cultured tumor cells (6). More recently, several polybasic peptides (so-called protein transduction domains, PTDs or cell-penetrating peptides, CPPs) have been shown to efficiently mediate uptake of nucleic acids, bioactive peptides, phage particles, and liposomes into a wide variety of mammalian cells. The initially proposed ability of CPPs to penetrate plasma membranes via a temperature-independent, non-endocytotic pathway was later shown to be a fixation artifact, and it is currently widely accepted that CPP-mediated macromolecular delivery follows energy-dependent endocytotic pathways that in most cases depend on the expression of cell-surface heparan sulfate proteoglycans (HSPGs) (7). 

Fig. 8.9 Current working model of endothelial lipase function. EL is synthesized by endothelial cells in variety of various tissues, is secreted and binds to HSPGs on the cell surface. There it binds to circulating lipoproteins, hydrolyzing phospholipids and resulting in lipoprotein particles that are reduced in phos-...

HSPG), possibly via syndecan-4, have been reported [76]. 

HS can be found in almost all animal cells. The lowest organisms where HS has been found are the metazoans ctenophora and cnidaria or jellyfish. "" HS chains are attached to HS proteoglycans (HSPGs) either on the cell surface or within the extracellular matrix. The amount and presence of HSPGs varies from cell to cell. An HSPG consists of a core protein to which the HS chains are attached. The core proteins are anchored to the cell... 

Figure 2 Schematic view of the HSPG. The core proteins are shown in coiored tubes whiie the HS chains are shown in black lines. The core protein of syndecan Is a transmembrane protein, with 3-5 attachment sites in the extraceiiuiar domain. The core protein of glypican attaches to the membrane through a glycosyi-phosphatidyiinositoi (GPi) anchor, with 1-3 HS attachment sites. The core protein of collagen Is not directly attached to the cell membrane it has three potentiai HS attachment sites.

Immunohistochemical methods have demonstrated molecules which may serve these functional specializations. Whereas antibodies to several components of BL (collagen type IV, laminin, nidogen, HSPG) stain both synaptic and extrasynaptic BL (Eldridge et al., 1986), other antibodies stain synaptic BL selectively, and still others stain... 

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