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Journal ArticleDOI

Catabolism of hyaluronan in rabbit skin takes place locally, in lymph nodes and liver.

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TLDR
The major part of the hyaluronan injected in the skin was, however, catabolized by lymphatic removal and subsequent degradation in local lymph nodes and liver.
Abstract
The catabolism of hyaluronan has been studied by injecting hyaluronan, labelled with 125I-tyramine cellobiose (125I-TC), subcutaneously into the hindpaw of rabbits. Following endocytosis, 125I-TC remains in the cells at the site of uptake, allowing localization of the site of catabolism. At 6 h after subcutaneous injection, 65% of the injected radioactivity was recovered. The skin at the injection site contained 47%, the popliteal gland at the side of injection 10%, and the liver 8% of the injected dose. At 48 h the three organs contained 40% of the injected dose with 17% in the skin, 10% in the lymph node and 13% in the liver. The decline in recovery could be accounted for by urinary excretion of the tracer, implying that some tracer had been released from the cells after endocytosis. Chromatography revealed that over 85% of 125I-TC-hyaluronan in the lymph nodes and liver was of low molecular mass throughout the experiment. In skin, 4% of the injected tracer was recovered with low molecular mass at 6 h, increasing to 12% of injected dose at 24 and 48 h. Thus, a minimum of 12% of the injected tracer was catabolized per 24 h at the skin injection site. If cells in skin are responsible for the subsequent release of tracer, as seen from the decrease in recovery of the injected dose, another 10-15% of the tracer could have been catabolized locally in the skin per day. The major part of the hyaluronan injected in the skin was, however, catabolized by lymphatic removal and subsequent degradation in local lymph nodes and liver.

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Citations
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Journal ArticleDOI

Hyaluronic acid: A key molecule in skin aging

TL;DR: Understanding the metabolism of HA in the different layers of the skin and the interactions of HA with other skin components will facilitate the ability to modulate skin moisture in a rational manner.
Journal ArticleDOI

Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory.

TL;DR: A mechanism-based rationale for the use of HA in some disease conditions with special reference to OA is provided, and the MW of HA appears to play a critical role in the formulation of the products used in the treatment of diseases.
Journal ArticleDOI

A recombinant human enzyme for enhanced interstitial transport of therapeutics

TL;DR: Depolymerization of the viscoelastic component of the interstitial matrix in animal models with a highly purified recombinant human hyaluronidase enzyme (rHuPH20) increased the dispersion of locally injected drugs, across a broad range of molecular weights without tissue distortion.
Journal ArticleDOI

Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration

TL;DR: A fully human recombinant DNA-derived hyaluronidase enzyme (rHuPH20) has been developed to leverage the historical efficacy of animal testes extract-derived spreading factors to reversibly modify the hypodermis, in light of discovery of the human hyaluranidase gene family.
Journal ArticleDOI

Hyaluronan Enters Keratinocytes by a Novel Endocytic Route for Catabolism

TL;DR: Rat epidermal keratinocytes internalize a large proportion of their newly synthesized hyaluronan into non-clathrin-coated endosomes in a receptor mediated way, and rapidly transport it to slower degradation in the endosomal/lysosomal system.
References
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Journal ArticleDOI

Proteoglycan-fibrillar collagen interactions

TL;DR: Interactions in connective tissues, including those between the proteoglycans and collagens are especially piquant, evolutionarily conserved and physiologically significant, and methods for diagnosing interactions are developed.
Journal ArticleDOI

Plasma clearance, tissue distribution and metabolism of hyaluronic acid injected intravenously in the rabbit

TL;DR: It is concluded that hyaluronic acid is removed from the plasma and degraded quickly by an efficient extrarenal system with a high reserve capacity, sited mainly in the liver.
Journal ArticleDOI

A radioiodinated, intracellularly trapped ligand for determining the sites of plasma protein degradation in vivo.

TL;DR: A simple double-label method was devised to provide a correction for intact protein in trapped plasma, the extravascular spaces, and within cells, and by using this method it becomes unnecessary to fractionate tissue samples.
Journal ArticleDOI

Scavenger functions of the liver endothelial cell.

TL;DR: It is shown that the liver endothelial cells make up an important part of the hepatic reticuloendothelial system in that they are specialized in receptor-mediated endocytosis of a number of macromolecules which are taken up only to a minor extent, or not at all, by other types of liver cells.
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