Specific Uptake of Succinylated Proteins Via a Scavenger Receptor-Mediated Mechanism in Cultured Brain Microvessel Endothelial Cells

Tokuda, Hideaki; Masuda, Seiji; Takakura, Yoshinobu; Sezaki, Hitoshi; Hashida, Mitsuru

doi:10.1006/bbrc.1993.2210

Cited by 26 publications

(12 citation statements)

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“…In our series of investigations, we have systematically studied the pharmacokinetics of macromolecules at the whole body, organ, and cellular levels by employing in vivo tissue distribution (Takakura et al, 1990(Takakura et al, , 1994aKawabata et al, 1995), in situ organ perfusion (Imoto et al, 1992;Nishida et al, 1992;Mihara et al, 1993;Takakura et al, 1994c), and in vitro cellular uptake (Tokuda et al, 1993;Takakura et al, 1994b) experiments, respectively. These studies have clarified the pharmacokinetic properties of the macromolecules in relation to their physicochemical characteristics, such as molecular weight and electric charge.…”

Section: Discussionmentioning

confidence: 99%

Renal Disposition Characteristics of Oligonucleotides Modified at Terminal Linkages in the Perfused Rat Kidney

Sawai¹,

Miyao²,

Takakura³

et al. 1995

Antisense Research and Development

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To clarify the renal disposition characteristics of oligonucleotides at the organ level, the renal handling of model end-capped oligonucleotides, 3'-methoxyethylamine 5'-biotin-decathymidylic acid containing phosphoramidate modifications at 3'- and 5'-terminal internucleoside linkages (T10) and its phosphorothioate (Ts10), were studied in the perfused rat kidney. In a single-pass indicator dilution experiment, venous outflow and urinary excretion patterns and tissue accumulation of radiolabeled oligonucleotides were evaluated under filtering or nonfiltering conditions. No significant binding to bovine serum albumin (BSA) in the perfusate was observed for T10, whereas more than 90% of Ts10 bound to BSA. The steady-state distribution volume of T10 calculated from the venous outflow pattern was larger than that of inulin, which corresponds to the extracellular volume of the kidney, whereas the distribution volume of Ts10 was larger than that of BSA (the intravascular volume). These results suggested their interaction with the vascular wall. Rapid urinary excretion was observed for T10, similar to inulin used as a marker of golmerular filtration rate. On the other hand, urinary excretion of Ts10 was greatly restricted due to its high binding ability (> 90%) to BSA in the perfusate. A significant amount of T10 and Ts10 was accumulated in the kidney (T10, 1.8% of injected dose; Ts10, 1.3%) compared with inulin (0.2%) and BSA (< 0.1%). The accumulation of these oligonucleotides was ascribed to both tubular reabsorption and uptake from the capillary side. In addition, the uptake of T10 from the capillary side was significantly inhibited by simultaneous injection of dextran sulfate, suggesting that the oligonucleotide was taken up as an anionic molecule. These findings will be useful information for the development of delivery systems for antisense oligonucleotides.

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Section: Discussionmentioning

confidence: 99%

Renal Disposition Characteristics of Oligonucleotides Modified at Terminal Linkages in the Perfused Rat Kidney

Sawai¹,

Miyao²,

Takakura³

et al. 1995

Antisense Research and Development

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“…The reasons behind this discrepancy are not clear, but may be related to the length of incubation time. The uptake of exogenously applied catalase by endothelial cells is a slow process ( Tokuda et al ., 1993 ). The usual incubation time with catalase used in most studies was around 30 min or less ( Auch‐Schwelk et al ., 1989 ; Nishimura et al ., 1995 ; Yang et al ., 2002 ), so that the amount of catalase entering endothelial cells in the arterial tissue may not be enough to scavenge a sudden surge of ACh‐triggered H 2 O 2 effectively.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide is an endothelium‐dependent contracting factor in rat renal artery

Gao

Lee

2005

British J Pharmacology

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1 In addition to endothelium-derived relaxing factor and hyperpolarizing factor, vascular endothelium also modulates smooth muscle tone by releasing endothelium-derived contracting factor(s) (EDCF), but the identity of EDCF remains obscure. We studied here the involvement of hydrogen peroxide (H 2 O 2 ) in endothelium-dependent contraction (EDC) of rat renal artery to acetylcholine (ACh). 2 ACh (10 À6 , 10 À5 , and 10 À4 M) induced a transient contraction of rat renal artery with intact endothelium in a concentration-related manner, but not in the artery with endothelium removed. In phenylephrine-precontracted renal arteries, ACh induced an endothelium-dependent relaxation response at lower concentrations (10 À8 -10 À6 M), and a relaxation followed by a contraction at higher concentrations (10 À5 M). Inhibition of nitric oxide synthase by N o -nitro-L-arginine (10 À4 M) enhanced the EDC to ACh. 3 Catalase (1000 U ml À1 ) reduced the EDC to ACh. H 2 O 2 (10 À6 , 10 À5 , and 10 À4 M) induced a similar transient contraction of the renal arteries as ACh, but in an endothelium-independent manner. Inhibition of NAD(P)H oxidase and cyclooxygenase by diphenylliodonium chloride and diclofenac greatly attenuated ACh-induced EDC, while inhibition of xanthine oxidase (allopurinol) and cytochrome P450 monooxygenase (17-octadecynoic acid) did not affect the contraction. Antagonist of thromboxane A 2 and prostaglandin H 2 receptors (SQ 29548) and thromboxane A 2 synthase inhibitor (furegrelate) attenuated the contraction to ACh and to H 2 O 2 . 4 In isolated endothelial cells, ACh (10 À5 M) induced a transient H 2 O 2 production detected with a fluorescence dye sensitive to H 2 O 2 (2 0 ,7 0 -dichlorofluorescein diacetate). The peak concentration of H 2 O 2 was 5.1 Â 10 À4 M at 3 min and was prevented by catalase. 5 Taken together, these results show that ACh triggers H 2 O 2 production through NAD(P)H oxidase activation in the endothelial cells, and that ACh and H 2 O 2 share the same signaling pathway in causing smooth muscle contraction. Therefore, H 2 O 2 is most likely the EDCF in rat renal artery in response to ACh stimulation.

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“…High-molecular-weight DS is capable of adsorbing specifically to several cell surface receptors, including scavenger receptors. It has also been shown to stimulate endocytosis in certain cell types (38) and to block endocytosis by competing with other molecules for the endocytic machinery (12,39,44). In an attempt to inhibit steps in endocytosis, we took advantage of observations that a low temperature blocks the movement of ligands between compartments of the endocytic pathway (13).…”

Section: Vol 71 1997mentioning

confidence: 99%

Dextran sulfate can act as an artificial receptor to mediate a type-specific herpes simplex virus infection via glycoprotein B

Dyer

Banfield

Martindale

et al. 1997

J Virol

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Herpes simplex virus (HSV) adsorption to host cells is mediated, at least in part, by the interaction of viral glycoproteins with cell surface glycosaminoglycans such as heparan sulfate and chondroitin sulfate. To investigate the contribution of various cell surface components in the infection pathway, we isolated a mutant cell line, sog9, which is unable to synthesize glycosaminoglycans (B. W. Banfield, Y. Leduc, L. Esford, K. Schubert, and F. Tufaro, J. Virol. 69:3290-3298, 1995). Although HSV-1 and HSV-2 infection of sog9 cells is diminished, the cells are still infected at about 0.5% efficiency, which suggests that these cells normally express at least one nonglycosaminoglycan receptor. In this report, we used sog9 cells to test whether glycosaminoglycan analogs, such as dextran sulfate (DS), could functionally substitute for cellular glycosaminoglycans to initiate HSV infection. We show that high-molecular-weight DS added either prior to or during inoculation stimulated HSV-1 but not HSV-2 infection by up to 35-fold; DS added after viral adsorption had no effect on infection efficiency. Moreover, DS stimulated HSV-1 infection at 4؇C, indicating that this compound impinged on an early, energy-independent step in infection. Using radiolabeled virus, we showed that HSV-1 is more efficient than HSV-2 in adsorbing to DS immobilized on microtiter wells. This raised the possibility that only HSV-1 could engage additional receptors to initiate infection in the presence of DS. To determine which viral component(s) facilitated DS stimulation, a panel of intertypic recombinants and deletion mutant viruses was investigated. These assays showed that DS stimulation of infection is mediated primarily by gB-1. Thus, this study provides direct evidence that a principal role for cell surface glycosaminoglycans in HSV infection is to provide an efficient matrix for virus adsorption. Moreover, by using DS as an alternative adsorption matrix (a trans receptor), we uncovered a functional, type-specific interaction of HSV-1 with a cell surface receptor.

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Specific Uptake of Succinylated Proteins Via a Scavenger Receptor-Mediated Mechanism in Cultured Brain Microvessel Endothelial Cells

Cited by 26 publications

References 0 publications

Renal Disposition Characteristics of Oligonucleotides Modified at Terminal Linkages in the Perfused Rat Kidney

Renal Disposition Characteristics of Oligonucleotides Modified at Terminal Linkages in the Perfused Rat Kidney

Hydrogen peroxide is an endothelium‐dependent contracting factor in rat renal artery

Dextran sulfate can act as an artificial receptor to mediate a type-specific herpes simplex virus infection via glycoprotein B

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