Modification of the carbohydrate in ricin with metaperiodate and cyanoborohydride mixtures: effect on binding, uptake and toxicity to parenchymal and non-parenchymal cells of rat liver

David N. Skilleter, Roger J. Price, Philip E. Thorpe

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The carbohydrate in the toxic glycoprotein ricin was chemically modified by simultaneous treatment with sodium metaperiodate and sodium cyanoborohydride. This treatment causes oxidative cleavage of the sugar residues and reduction of the aldehyde groups which are formed to primary alcohols. The modification markedly decreased the rapid removal of ricin from the blood by hepatic non-parenchymal cells with only a relatively small increase in accumulation of the toxin by parenchymal cells. Binding, uptake and toxicity of the modified ricin in primary monolayer cultures of hepatic non-parenchymalcells were all decreased to a much greater extent than in parenchymal cells. The results indicate that native ricin binds to non-parenchymal cells by a dual recognition process which involves both interaction of cell receptors with the mannose-containing oligosaccharides of the toxin and binding of ricin to galactose-containing glycoproteins and glycolipids on the cells. However, uptake and toxicity of native ricin in non-parenchymal cells appears to result principally from entry of the toxin through the mannose recognition pathway. By contrast, uptake and toxicity of the modified ricin in non-parenchymal cells, and of both ricin and the modified toxin in parenchymal cells, is expressed essentially through the galactose-recognition route.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalBBA - General Subjects
Volume842
Issue number1
DOIs
StatePublished - Sep 27 1985

Fingerprint

Ricin
Liver
Toxicity
Rats
Cells
Carbohydrates
Mannose
Galactose
Glycoproteins
metaperiodate
Poisons
Glycolipids
Oligosaccharides
Aldehydes
Cell Communication
Sugars
Monolayers
Blood
Alcohols

Keywords

  • (Hepatic parenchymal, non-parenchymal cells)
  • Chemical modification
  • Ricin accumulation
  • Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Modification of the carbohydrate in ricin with metaperiodate and cyanoborohydride mixtures : effect on binding, uptake and toxicity to parenchymal and non-parenchymal cells of rat liver. / Skilleter, David N.; Price, Roger J.; Thorpe, Philip E.

In: BBA - General Subjects, Vol. 842, No. 1, 27.09.1985, p. 12-21.

Research output: Contribution to journalArticle

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AB - The carbohydrate in the toxic glycoprotein ricin was chemically modified by simultaneous treatment with sodium metaperiodate and sodium cyanoborohydride. This treatment causes oxidative cleavage of the sugar residues and reduction of the aldehyde groups which are formed to primary alcohols. The modification markedly decreased the rapid removal of ricin from the blood by hepatic non-parenchymal cells with only a relatively small increase in accumulation of the toxin by parenchymal cells. Binding, uptake and toxicity of the modified ricin in primary monolayer cultures of hepatic non-parenchymalcells were all decreased to a much greater extent than in parenchymal cells. The results indicate that native ricin binds to non-parenchymal cells by a dual recognition process which involves both interaction of cell receptors with the mannose-containing oligosaccharides of the toxin and binding of ricin to galactose-containing glycoproteins and glycolipids on the cells. However, uptake and toxicity of native ricin in non-parenchymal cells appears to result principally from entry of the toxin through the mannose recognition pathway. By contrast, uptake and toxicity of the modified ricin in non-parenchymal cells, and of both ricin and the modified toxin in parenchymal cells, is expressed essentially through the galactose-recognition route.

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