Uptake and intracellular fate of gelonin, a ribosome-inactivating protein, in rat liver

Melwin Colaço, M. M. Bapat, Sandra Misquith, Michel Jadot, Simone Wattiaux-De Coninck, Robert Wattiaux

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Gelonin, a type 1 ribosome-inactivating protein, has been used as toxin conjugate for several therapeutic purposes. We have investigated the endocytosis of gelonin by rat liver in vivo. Subcellular distribution of [125I]gelonin was established after differential and isopycnic centrifugation. Fractions were analyzed for acid-soluble and acid-precipitable radioactivity. Results show that gelonin is rapidly cleared from the blood and within 15 min reaches a peak (25% of total injected) in the liver. With time, radioactivity associated with the liver markedly decreases. Two important observations are made: (a) Radioactivity associated with all fractions, at any time point, is greater than 80% acid precipitable. (b) Even at 5 min, a significant amount of intact gelonin is present in the cytosolic fraction. Our work suggests that, though gelonin is rapidly cleared from the blood, there are still intact molecules that have entered the cytosol where they could exert their toxic effect.

langue originaleAnglais
Pages (de - à)1180-1185
Nombre de pages6
journalBiochemical and Biophysical Research Communications
Numéro de publication5
Les DOIs
Etat de la publicationPublié - 14 oct. 2002

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