Comparison of glucosylated low density lipoprotein with methylated or cyclohexanedione-treated low density lipoprotein in the measurement of receptor-independent low density lipoprotein catabolism

Abstract

We previously showed that glucosylation of lysine residues of low density lipoprotein (LDL) blocks high-affinity degradation by cultured human fibroblasts, and markedly slows LDL turnover in guinea pigs. The present studies were done to evaluate glucosylated (GLC) LDL as a tracer of receptor-independent LDL catabolism, and to compare it with two other modified LDL, methylated (MT) LDL, and cyclohexanedione (CHD)-treated LDL, which have been used previously for this purpose. Glucosylation of LDL did not affect receptor-independent degradation in vivo, as the turnover of GLC-LDL and native LDL were similar in the LDL receptor-deficient, Watanabe heritable hyperlipidemic rabbit. Each modified radiolabeled LDL preparation was injected into eight guinea pigs, and fractional catabolic rates (FCR) determined. The FCR of GLC-LDL (0.024 ± 0.005 h-1; SD) was similar to that of MET-LDL (0.023 ± 0.006 h-1), and ~22% of that of native LDL (0.105 ± 0.02 h-1). The FCR of CHD-LDL was greater than that of the other modified LDL, and it varied depending on how soon after preparation the CHD-LDL was injected: when used within 2 h of preparation, the mean FCR was 0.044 ± 0.007 h-1 (n = 4); when used after overnight dialysis at 4°C, the mean FCR was 0.082 ± 0.03 h-1 (n = 4). This suggests that CHD-LDL overestimates the amount of LDL degraded by receptor-independent pathways, perhaps because the CHD modification is spontaneously reversible. The present studies indicate that GLC-LDL is a useful tracer of receptor-independent LDL catabolism in animals.