Metabolism of homologous and heterologous lipoproteins by cultured rat and human skin fibroblasts.
Metabolism of homologous and heterologous lipoproteins by cultured rat and human skin fibroblasts.
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发表时间：
1981
影响因子：
6.5
通讯作者：
C. Drevon;A. Attie;S. Pangburn;D. Steinberg
中科院分区：
文献类型：
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作者：
C. Drevon;A. Attie;S. Pangburn;D. Steinberg
大鼠成纤维细胞降解人低密度脂蛋白（LDL）非常缓慢，十分之一到四十分之一的人成纤维细胞中观察到的速率。在大鼠细胞中，人LDL仅引起细胞胆固醇含量和酰基辅酶A：胆固醇酰基转移酶（ACAT）活性的非常小的增加，并且仅引起β-羟基-β-甲基戊二酰辅酶A（HMG CoA）还原酶活性的小幅度降低;然而，在人细胞中，人LDL诱导了所有三个参数的非常大的变化，正如预期的那样。人低密度脂蛋白与大鼠成纤维细胞的结合并没有减少先前与人低密度脂蛋白或25-羟基胆固醇孵育。因此，在大鼠成纤维细胞中，似乎很少有（如果有的话）识别人LDL的受调节的高亲和力受体。与此相反，大鼠LDL组分（d 1.02-1.05 g/ml），大鼠成纤维细胞比人LDL降解更快，导致细胞胆固醇含量显着增加，ACAT活性增加，HMG CoA还原酶活性显着降低。此外，大鼠成纤维细胞对该大鼠LDL组分的降解作为浓度的函数是双相的，即，似乎存在高亲和力降解组分。因此，看来大鼠成纤维细胞确实具有同源脂蛋白的受体。然而，由于载脂蛋白B和载脂蛋白E都存在于这些大鼠脂蛋白组分中，所观察到的效应可能与这些载脂蛋白中的一种或两种的识别有关。大鼠或人成纤维细胞对大鼠常规定义的高密度脂蛋白（HDL）组分的代谢和代谢效应与人成纤维细胞中人LDL的代谢和代谢效应相似。结果表明，大鼠HDL由于其载脂蛋白E含量和血浆中相对于LDL的较高浓度，可能在体内胆固醇稳态中起重要作用。
Rat fibroblasts degraded human low density lipoprotein (LDL) very slowly, one-tenth to one-fortieth the rates observed in human fibroblasts. In rat cells, human LDL caused only very small increases in cell cholesterol content and acylCoA:cholesterol acyltransferase (ACAT) activity and caused only small decreases in beta-hydroxy-beta-methylglutaryl CoA (HMG CoA) reductase activity; in human cells, however, human LDL induced very large changes in all three of these parameters, as expected. The binding of human LDL to rat fibroblasts was not reduced by previous incubation with human LDL or with 25-hydroxycholesterol. Thus, in rat fibroblasts there appear to be few, if any, regulated high-affinity receptors that recognize human LDL. Rat LDL fractions (d 1.02-1.05 g/ml), in contrast, were degraded more rapidly than human LDL by rat fibroblasts, caused a significant increase in cell cholesterol content, an increase in ACAT activity, and a significant decrease in HMG CoA reductase activity. Moreover, the degradation of this rat LDL fraction by rat fibroblasts as a function of concentration was biphasic, i.e., there appeared to be a high-affinity component of degradation. Thus, it appears that rat fibroblasts do have a receptor for homologous lipoproteins. However, because both apoprotein B and apoprotein E are present in these rat lipoprotein fractions, the observed effects may relate to recognition of either or both of these apoproteins. The metabolism and metabolic effects of the conventionally defined high density lipoprotein (HDL) fraction of the rat by rat or human fibroblasts resembled those of human LDL in human fibroblasts. It is suggested that rat HDL may, because of its apo E content and higher concentration in rat plasma relative to that of LDL, play an important role in cholesterol homeostasis in vivo.