Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ricin A chain has previously been shown to intoxicate macrophages in vitro following binding and endocytosis by the macrophage mannose receptor. In this report it is demonstrated that the intravenous injection of ricin A chain in nephrectomized rats leads to a prolonged plasma half-life for [125I]beta-glucuronidase, a ligand for the mannose receptor. Clearance of [125I]asialofetuin, a ligand for the galactose receptor of hepatocytes, was unaffected by injection of A chain. Microscopic examination of the livers of A chain-treated animals revealed a loss of phagocytic cells from the liver sinusoids. These results suggest that ricin A chain may be useful as a toxin specific for mannose receptor bearing cells of the reticuloendothelial system.
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PMID:In vivo depletion of mannose receptor bearing cells from rat liver by ricin A chain: effects on clearance of beta-glucuronidase. 244 98

We used the A-chain of the toxin ricin (RTA) as a toxin specific to Kupffer cells in mice. RTA is specifically taken up by the mannose receptor present exclusively in macrophages. Kupffer cells were quantitated by shifts in beta-glucuronidase clearance and microscopic counts of cells which phagocytosed India ink. When compared to saline controls, 20 mg/kg of RTA intraperitoneally (divided over 4 days) or intraportally (single doses) significantly prolonged the t 1/2 half-life of beta-glucuronidase by 270 +/- 37 and 210 +/- 8%, respectively. Kupffer cell numbers were significantly decreased by 27 +/- 8 and 33 +/- 16%. This effect persisted for at least 3 days after toxin administration. Despite effects on Kupffer cell number, minimal histological damage to liver, spleen, lung, and heart was noted. Higher doses of RTA or doses potentiated by ureteral ligation to prevent renal clearance resulted in prohibitive mortalities and histologic liver damage. Doses of Hura crepitans inhibitor, a toxin similar to RTA but not mannose-receptor specific, did not affect Kupffer cell numbers. We conclude that RTA given both intraperitoneally and intraportally at low doses is toxic specifically to Kupffer cells. Kupffer cell numbers can be indirectly measured by beta-glucuronidase clearance.
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PMID:Use of ricin A-chain to selectively deplete Kupffer cells. 339 96

Chloroquine-resistant (CQr) clones (CQ-21 and CQ-22) have been isolated from mutagenized hamster lung V79 cells by exposing the cells to a high dose of chloroquine. CQ-21 and CQ-22 showed about 3-fold higher resistance to chloroquine than the parental V79 cells, and they showed specific cross-resistance to another amine, NH4Cl, which is also concentrated in lysosomes. CQr clone showed no cross-resistance to other unrelated agents. Chloroquine-induced inhibition of [125I]ricin internalization was observed in both cell lines at neutral pH, but the inhibition of uptake was less in the variant. Also, the degradation of endogenous protein was slowed in the mutant; further, treatment of cells with 30 micrograms/ml of chloroquine inhibited the degradation of endogenous proteins in the parental V79, but not in CQ-22 cells. Similar levels of acid phosphatase, beta-glucuronidase and cathepsin D were observed in V79 and CQ-22 cells, but the level of cathepsin B was lower in the mutant. Electron microscopy showed an increased number of electron-dense bodies, possibly autophagosomes/lysosomes, in the mutant cells grown for 4 days with 5 micrograms/ml of chloroquine. Similar aberrant structures were observed in the parental V79 cells treated for only 3 h with 5 micrograms/ml of chloroquine.
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PMID:Isolation of chloroquine-resistant Chinese hamster V79 cell variants that are also resistant to ammonium chloride. 665 68