Comparative effects of diabetes and monensin on the lectin asialoglycoprotein receptor: biosynthesis, structure and function in rats.
The hepatic asialoglycoprotein receptor is the first studied mammalian lectin. Modulations in vivo by diabetes and in vitro by the carboxylic ionophore monensin gave rise to similar apparent alterations on its biosynthesis, structure and ligand binding capacity. In normal rats, the receptor (whether purified by ligand or antibody-affinity chromatography) presented a similar pattern in SDS-PAGE analysis, with a major 42-kDa band and two minor ones (49 and 52-54 kDa). In diabetic rats, a new 38-kDa band appeared, but only after antibody-affinity purification. In vitro biosynthesis of the receptor by normal hepatocytes in the presence of 35S-methionine showed that this 38-kDa band was present at the end of a 30-min pulse but decreased during a 180-min chase, in association with an increase in the major 42-kDa band. In diabetic cells, this evolution was retarded. Using a 30-min pulse followed by a 120-min chase in the presence of 100 microM monensin, we showed that this carboxylic ionophore had similar effects on diabetes, leading to a delay in the maturation process of the 42-kDa band and the persistent emergence of the 38-kDa species. Allowing incubation in the presence of 25 or 100 microM monensin, we observed a decrease in the number of ligand binding sites both at the surface (40%) and within the cell (28%). In hepatocytes from diabetic rats, monensin showed no additional effect on the partial diabetes-induced inactivation.
Slama
A
A
Laboratoire de Biochimie, UFR des Sciences Pharmaceutiques, Université Paris-Sud, Châtenay-Malabry, France.
Gil-Falgon
S
S
Agneray
J
J
Feger
J
J
D000818:Animals; D037263:Asialoglycoprotein Receptor; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism
D037263:Asialoglycoprotein Receptor; D037102:Lectins; D011971:Receptors, Immunologic; D008985:Monensin