Intracellular distribution of radiogold. Localization to large granule membranes

Penneys, Neal S.; McCreary, B S Sally; Gottlieb, Norman L.

doi:10.1002/art.1780190515

Cited by 29 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The subcellular distribution of gold, particularly in the livers and the cortex, showed relatively larger increases in the lysosomal fractions. These increases may partly be attributable to autophagocytosis and partly to the relatively high uptake of gold by the endocytic Kupffer cells of the liver (Penneys et al, 1976) and the proximal tubular epithelial cells of the kidney (Vernon -Roberts et al, 1976). The active uptake of gold by the tissues was much more striking in the kidney cortex than elsewhere.…”

Section: Discussionmentioning

confidence: 99%

“…The subcellular distribution of gold compounds in tissues (Lawson et al, 1974) showed a relatively high concentration of gold in lysosomal bodies. Furthermore Penneys, McCreary & Gottlieb (1976) demonstrated that in the Kupffer cells of rat liver, 95% of the gold associated with the lysosomes was localised in the organelle membranes. The interactions of gold with the lysosomal enzymes and its localisation in the membranes suggested sodium aurothiomalate may act by inhibiting lysosomal enzymes and/or stabilising lysosomal membranes.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

The subcellular distribution of gold in monkey liver, kidney and spleen, in vivo

Shaima

McQueen

1979

Clin Exp Pharmacol Physiol

View full text Add to dashboard Cite

1. The subcellular distribution of gold in the livers, kidney cortex and the spleens of rhesus monkeys was determined at 2, 10 and 20 days after the administration of sodium (195Au)-aurothiomalate. The serum gold levels were also determined over the period of study. 2. With the continued decrease in the serum gold levels from day 1 to day 20, a continued increase in the tissue levels of the organs studied was observed. The corresponding subcellular fractions of the tissues also showed continued increases in the radioactive concentrations of gold. 3. Gold was found to localise in all the organelles of the cells in the liver, kidney cortex and the spleen, though in varying amounts. The largest increases in the concentrations of gold from day 2 to day 20 were found in the lysosomal bodies of liver and kidney. The concentrations in the kidney cortex increased from approximately five times those in the liver or the spleen on day 2 to about eight times those on day 20.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

The subcellular distribution of gold in monkey liver, kidney and spleen, in vivo

Shaima

McQueen

1979

Clin Exp Pharmacol Physiol

View full text Add to dashboard Cite

show abstract

“…Although the exact mode of their action is still unknown, a number of hypotheses have been proposed to explain the effectiveness of gold; these include inhibition of lysosomal enzymes [3,4], increasing collagen cross-linking [5,6], inhibition of macrophage and neutrophil phagocytosis [7,8], inactivation of complement [9,10], inhibition of lymphocyte proliferation and of neutrophil chemotaxis [11,12].…”

Section: Introductionmentioning

confidence: 99%

Metabolism of intracellular zinc and copper following single and repeated injections of gold sodium thiomalate

1983

Agents and Actions

View full text Add to dashboard Cite

Repeated injections of gold sodium thiomalate were given to Wistar rats and the effect of gold on the binding of endogenous zinc and copper to the cytosolic proteins in the liver and kidneys was studied. The tissue levels of gold and the tissue uptake of zinc and copper as a function of gold dose was also studied.The result of the multiple-dose study show that in the liver the tissue gold levels rose rapidly following the first five gold injections (one injection/week) and then stabilized. In the kidneys the gold concentrations continued to increase with each additional dose. Uptake of zinc into the high molecular weight proteins (MW > 60,000 daitons) and the supernxide dismutase fractions were significantly increased following the repeated gold injections in the liver and kidney cytosoi. The uptake of copper into the high MW proteins were decreased in the liver as well as the kidneys. Copper levels in the superoxide dlsmutase and the low MW (< 4000 daltons) fractions initially increased then decreased from the sixth gold dose onwards (possibly related to the overall decrease in tissue copper levels in the liver). The incorporation of eopper into the hepatie metallothioneins appeared to be unaltered. In the kidney eytosol, the uptake of copper was significantly increased into the metallothionein fractions. The uptake into the other fractions decreased over the multiple-dose period.Gold sodium thlomalate inereased the tissue eoncentratlon of zinc in the liver as well as the kidneys. The level of copper in the liver was decreased and that in the kidneys increased. Practically all the additional copper in the kidneys was incorporated in the thioneins.These observations indieate that gold sodium thiomalate has a major role in providing a stimulus for the liver, kidney and perhaps other cells to bring about a redistribution of body zlne and copper. The various cytosolic proteins, including the inducible metalloproteins, superoxide dismutase and metallothioneins, seem to help the cell carry out this task. In view of the importanee of these essential metals in physiological processes of relevance to rheumatoid arthritis, it is suggested that gold salts may mediate, to some extent, their antiarthrltic activity through an effect on the metabolism of zinc and copper.

show abstract

“…However, its mechanism of action remains unknown. Histopathologic studies have shown that gold accumulates within lysosomes of mononuclear phagocytes (17)(18)(19)(20). After prolonged chrysotherapy, more than 50% of total body elemental gold may be found in the liver, lymph nodes, spleen, and bone marrow.…”

mentioning

confidence: 99%

Effects of gold sodium thiomalate on interferon stimulation of C2 synthesis and HLA–DR expression by human monocytes

Sanders

Carlson

Littman

1987

Arthritis & Rheumatism

View full text Add to dashboard Cite

Gamma-interferon ( y-IFN) is a T cell-derived lymphokine that has potent macrophage-activating properties. It increases Fc receptor density, increases the formation and release of reactive oxygen intermediates, increases the synthesis and release of complement cascade proteins, especially C2 and factor B, and increases class I1 (HLA-DR) antigen expression. These effects may play a role in the potentiation of inflammation in rheumatoid arthritis. We examined the possibility that gold sodium thiomalate (GST), an effective treatment for rheumatoid arthritis, would inhibit y-IFN-mediated stimulation of monocyte/macrophages. GST in concentrations attainable in vivo was shown to inhibit both spontaneous and yIFN-stimulated C2 production up to 50%. GST inhibition could be only partially overcome with increasing concentrations of y-IFN. In addition, GST inhibited y-IFN-stimulated Thomas Fund publication no. 242.

show abstract

Intracellular distribution of radiogold. Localization to large granule membranes

Cited by 29 publications

References 36 publications

The subcellular distribution of gold in monkey liver, kidney and spleen, in vivo

The subcellular distribution of gold in monkey liver, kidney and spleen, in vivo

Metabolism of intracellular zinc and copper following single and repeated injections of gold sodium thiomalate

Effects of gold sodium thiomalate on interferon stimulation of C2 synthesis and HLA–DR expression by human monocytes

Contact Info

Product

Resources

About