Galactose-specific asialoglycoprotein receptor is involved in lipoprotein (a) catabolism.
Lp(a) [lipoprotein (a)] is a highly atherogenic plasma lipoprotein assembled from low-density lipoprotein and the glycoprotein apolipoprotein (a). The rate of Lp(a) biosynthesis correlates significantly with plasma Lp(a) concentrations, whereas the fractional catabolic rate does not have much influence. So far, little is known about Lp(a) catabolism. To study the site and mode of Lp(a) catabolism, native or sialidase-treated Lp(a) was injected into hedgehogs or ASGPR (asialoglycoprotein receptor)-knockout (ASGPR-) mice or wild-type (ASGPR+) mice, and the decay of the plasma Lp(a) concentration was followed. COS-7 cells were transfected with high- (HL-1) and low-molecular-mass ASGPR subunits (HL-2), and binding and degradation of intact or desialylated Lp(a) were measured. In hedgehogs, one of the few species that synthesize Lp(a), most of the Lp(a) was taken up by the liver, followed by kidney and spleen. Lp(a) and asialo-Lp(a) were catabolized with apparent half-lives of 13.8 and 0.55 h respectively. Asialo-orosomucoide increased both half-lives significantly. In mice, the apparent half-life of Lp(a) was 4-6 h. Catabolism of native Lp(a) by wild-type mice was significantly faster compared with ASGPR- mice and there was a significantly greater accumulation of Lp(a) in the liver of ASGPR+ mice compared with ASGPR- mice. The catabolism of asialo-Lp(a) in ASGPR- mice was 8-fold faster when compared with native Lp(a) in wild-type mice. Transfected COS-7 cells expressing functional ASGPR showed approx. 5-fold greater binding and 2-fold faster degradation of native Lp(a) compared with control cells. Our results for the first time demonstrate a physiological function of ASGPR in the catabolism of Lp(a).
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D005260:Female; D005690:Galactose / Q000378:metabolism; D006364:Hedgehogs / Q000378:metabolism; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009439:Neuraminidase / Q000378:metabolism; D014170:Transformation, Genetic
D037263:Asialoglycoprotein Receptor; D017270:Lipoprotein(a); D009439:Neuraminidase; D005690:Galactose