Acetyl-low density lipoprotein receptors on rat mesangial cells

Suzaki, Kyoichi; Kobori, Shozo; Ide, Masaya; Sasahara, Takayuki; Sakai, Masakazu; Toyonaga, Tetsushi; Shinohara, M; Miyazaki, Akira; Horiuchi, Seikoh; Takeda, Haruo; Shichiri, Motoaki

doi:10.1016/0021-9150(93)90114-a

Cited by 13 publications

(2 citation statements)

References 18 publications

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“…The mesangial cells have been reported to be involved in endocytosis of macromolecules (Schlondorff, 1987). Recently, acetyl-low density lipoprotein (Suzaki et al, 1993) and oxidized low density protein receptors (Lee and Koh, 1994) have been found on rat cultured mesangial cells. These findings suggest that rat mesangial cells may have a scavenger function similar to that of macrophages, which have scavenger receptors for polyanionic macromolecules with unusually broad but circumscribed ligand binding specificity (Pearson et al, 1993).…”

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 experimental protocol was approved by the Human Ethics Review Committee of our institution and a signed consent form was obtained from each patient. Human glomeruli were isolated according to the method of Gröne et al [13], with minor modifications [14,15]. Briefly, the kidneys of patients with ureteral cancer were removed and the cortices of normal sections were cut and pressed through a series of sieves of decreasing pore size (250, 125 and 110 m).…”

Section: Cellsmentioning

confidence: 99%