Asialoglycoprotein receptor is uninvolved in clearing intact glycoproteins from rat blood

Abstract

The hypothesis that the hepatic receptor for asialoglycoproteins would mediate turnover of glycoproteins in blood (after their desialylation by neuraminidase located on cell surfaces) was tested in rats by measuring clearance of intact 125I-labeled glycoproteins in the presence or absence of enough unlabeled asialoglycoproteins to saturate the asialoglycoprotein receptor. Via an indwelling venous catheter, a mixture of 125I-orosomucoid (obtained from rat serum) and a bolus of unlabeled asialofetuin (bovine) was injected, and infusion of an asialofetuin solution sustained. Total radioactivity and trichloroacetic acid-precipitable radioactivity were measured in blood samples taken at frequent intervals from an arterial catheter. Clearance was computer analyzed by using a two-component model. Nondestructiveness of radiolabeling and desialylation methods and interchangeability of rat and bovine (asialo)glycoproteins were demonstrated in control experiments. The infusion trials showed that independent clearance processes exist for intact and asialoglycoproteins. Apparently, the asialoglycoprotein receptor has no function in the turnover of intact plasma glycoproteins.

Hierarchy of Post-translational Modifications Involved in the Circulatory Longevity of Glycoproteins

“…In contrast to the wealth of data concerning the possible effects of sialic acid removal on the circulatory longevity of glycoproteins (7)(8)(9)(31)(32)(33)(34)(35)(36), there is very limited information on the involvement of ␣-gal-capped glycans in determining the circulatory behavior of glycoproteins. To examine this issue, the intact FBS-AChE enzyme was subjected to extensive ␣-galactosidase treatment (see "Materials and Methods").…”

Erythropoiesis stimulating agents approaches to modulate activity

“…For example, the clearance of rHuEPO in normal and liver cirrhosis patients was not different suggesting that liver ASGPR may not play a significant role in rHuEPO clearance 46,47,49,50. Other studies have also supported the finding that the liver may not play a key role in asialoprotein clearance: the saturation of the ASGPR with asialoorosomucoid did not delay the clearance of sialylated 125 I-orosomucoid51 and no accumulation of desialylated glycoproteins or lipoproteins were reported in ASGPR knockout mouse circulation, though reduced clearance rates of asialoorosomucoid or asialofetuin were reported 52,53…”

Role of Carbohydrate in Glycoprotein Traffic and Secretion

“…Numerous investigators have shown in many systems that desialylated glycoproteins, when injected into mammals, are rapidly removed from serum by this receptor in liver. However, four laboratories have shown that under normal circumstances serum glycoproteins are not desialylated in vivo and are not cleared from the circulation by this receptor (Wong et al, 1974;Clarenburg, 1983;Kuranda and Aronson, 1983;Lefort et al, 1984).…”