Endothelial cells, membrane proteins

Detailed photochemical studies of RBS and RRS have revealed that the photolysis of RRS produces RBS and NO quantitatively (Scheme 5.6) and the RBS produced undergoes further photodecomposition to generate NO and iron (III) [165, 168]. RBS has been tested as an NO delivery drug to the vascular and brain tissues by thermal as well as photochemical means [169, 170]. Due to the high solubilities in aprotic solvents, Roussin s salts are able to penetrate the endothelial cell membrane easily and deliver NO for hours [169]. RBS has been found to inhibit ADP-induced platelet aggregation [171] and Roussin s salts in general show a bacteriostatic effect, presumably due to the interaction of released NO and iron-sulfur proteins [172]. 

Most endothelial cell membranes are ordinarily impermeable to proteins. Transport across these barriers occurs only with the aid of receptor-mediated or other transport processes. However, many active sites (receptors) are located on cell surfaces and there is no need to permeate the cell. To achieve an adequate intracellular concentration, relatively large amounts of protein must be administered. Proteins administered by nonparenteral means and intended for systemic effects, such as intranasally and directly into the lungs. 

A. H. Stolpen, D. E. Golan, and J. S. Pober, Tumor necrosis factor and immune interferon act in concert to slow the lateral diffusion of proteins and lipids in human endothelial cell membranes, J. Cell Biol. 707 781-789 (1988). 

Bovine adrenal capillary endothelial cells Membrane-based patterning of protein, BSA backfill 2000 [92]... 

Horvat R et al (1986) Endothelial cell membranes contain podocalyxin—the major sialo-protein of visceral glomerular epithelial cells. J Cell Biol 102(2) 484-491... 

N. V. Ketis, R. L. Hoover, and M. J. Kamovsky. Isolation of bovine aortic endothelial cell membranes. Identification of membrane associated cytoskeletal proteins. J. Cell Biol. 725 162-171 (1986). 

Rather uniquely, ICAM-1 is also subverted as receptor by human pathogens in at least three different ways. Major group rhinoviruses and A-type coxsackieviruses use ICAM-1 to release their RNA into the host cell cytoplasm. Erythrocytes infected by the malarial parasite Plasmodium falciparum, are able to bind ICAM-1 in the surface of endothelial cells (Berendt et al., 1992 Ockenhouse et al., 1992), and use this cytoadherence to sequester themselves in deep vascular beds, including the brain, minimizing exposure of the parasite to immune surveillance. Finally, human immunodeficiency virus-1 (HIV-1), uses ICAM-1 as a coreceptor (Bastiani et al., 1997 Fortin et al., 1997 Rizzuto and Sodroski, 1997). HIV-1 acquires several host cell membrane proteins when it buds from infected cells, making it possible for ICAM-1 to be incorporated into the envelope of the virions. This results in an increase of subsequent virus-cell interactions, enhancement of virus infectivity, and extension of the host cell range. 

In multicellular organisms, thin lipid membranes serve as semipermeable barriers between aqueous compartments (Figure 5.1). The plasma membrane of the cell separates the cytoplasm from the extracellular space endothelial cell membranes separate the blood within the vascular space from the rest of the tissue. Properties of the lipid membrane are critically important in regulating the movement of molecules between these aqueous spaces. While certain barrier properties of membranes can be attributed to the lipid components, accessory molecules within the cell membrane—particularly transport proteins and ion channels—control the rate of permeation of many solutes. Transport proteins permit the cell to regulate the composition of its intracellular environment in response to extracellular conditions. 

Multiple cellular effects of D-fructose-albumin imply the existence of specific cellular receptors for this molecule, and a search for such receptors has identified so far a number of such sites on monocytes, peritoneal and alveolar macrophages, endothelial cells, and fibroblasts. Cell-membrane proteins that may interact with D-fructose-albumin through its A/ -D-fiuctose-L-lysine epitopes include nucleolin, myosin heavy chain, and calnexin. ... 

The protein-C pathway is one of the most important anticoagulant mechanisms. It is activated by thrombin. Thrombin binds to a cofactor in the membrane of endothelial cells, thrombomodulin (TM). TM bound thrombin no longer activates clotting factors or platelets but becomes an effective protein C (PC) activator. Activated PC (APC) forms a complex with Protein S, which inactivates FVIIIa and FVa. Hereby generation of Flla by the prothrombinase complex is inhibited (Fig. 9). Thus, the PC-pathway controls thrombin generation in a negative feedback manner. 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

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