TY - JOUR
T1 - Uptake and intracellular fate of gelonin, a ribosome-inactivating protein, in rat liver
AU - Colaço, Melwin
AU - Bapat, M. M.
AU - Misquith, Sandra
AU - Jadot, Michel
AU - Wattiaux-De Coninck, Simone
AU - Wattiaux, Robert
PY - 2002/10/14
Y1 - 2002/10/14
N2 - 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.
AB - 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.
KW - Endocytosis
KW - Gelonin
KW - Liver
KW - Rat
KW - Ribosome-inactivating protein
UR - http://www.scopus.com/inward/record.url?scp=0036387122&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(02)02068-5
DO - 10.1016/S0006-291X(02)02068-5
M3 - Article
C2 - 12207898
AN - SCOPUS:0036387122
SN - 0006-291X
VL - 296
SP - 1180
EP - 1185
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 5
ER -