ALTERATIONS IN METABOLIC ACTIVITY OF PLASMA LIPOPROTEINS FOLLOWING SELECTIVE CHEMICAL MODIFICATION OF THE APOPROTEINS

ALTERATIONS IN METABOLIC ACTIVITY OF PLASMA LIPOPROTEINS FOLLOWING SELECTIVE CHEMICAL MODIFICATION OF THE APOPROTEINS
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脱氧蛋白选择性化学修饰后血浆脂蛋白代谢活性的变化

DOI:
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发表时间:
1980
影响因子:
5.2
通讯作者:
K. Weisgraber
K. Weisgraber
中科院分区:
综合性期刊3区
文献类型:
--
作者:
R. Mahley;T. Innerarity;K. Weisgraber

文献摘要

被引文献

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体内部位的识别和血浆脂蛋白及其胆固醇的摄取和代谢机制的阐明仍然是需要研究的重要问题。脂蛋白催化剂的控制对脂质代谢和动脉粥样硬化的发生具有重要意义。现在已经确定,不同类型的细胞(成纤维细胞、白细胞、肝细胞、肾上腺皮质细胞等)能够与特定的血浆脂蛋白相互作用。在研究这些过程中,我们的注意力一直集中在脂蛋白的蛋白质部分作为负责与细胞相互作用的决定因素。这些研究依赖于使用具有特定脂质和载脂蛋白成分的各种血浆脂蛋白。包括人在内的各种物种的低密度脂蛋白(LDL)几乎只含有脱辅基蛋白B。另一类有用的脂蛋白,其脂质组成和颗粒大小与LDL相似,已在各种动物的血浆中鉴定。这些脂蛋白与高密度脂蛋白(HDL)相关,分别在对照组和胆固醇喂养的犬、大鼠和猪中称为HDL和HDL。1 -6 HDL和HDL部分出现在低密度范围内,但与LDL明显不同,因为它们缺乏B载脂蛋白。它们含有E和A-I载脂蛋白或仅含有E载脂蛋白,后者称为apoE HDL。这些脂蛋白存在于人血浆中,并且在胆固醇喂养后它们的浓度似乎增加。6,通过比较这些特定脂蛋白的体外和体内代谢,研究了特定载脂蛋白的作用,包括含有载脂蛋白B的LDL,仅含有载脂蛋白E的HDL(apoE HDL)和主要含有A-I(或A-I和A-11)脱辅基蛋白而不含E脱辅基蛋白的HDL。这些脂蛋白的赖氨酸和精氨酸残基的选择性化学修饰已被用于探测脂蛋白细胞相互作用的性质,在体外培养的细胞和在体内的各种动物静脉注射后。
Identification of the sites within the body and elucidation of the mechanisms responsible for the uptake and catabolism of the plasma lipoproteins and their cholesterol remain important questions which need to be studied. Control of lipoprotein catabolism has important implications for lipid metabolism and atherogenesis. It is now established that different cell types (fibroblasts, leukocytes, hepatocytes, adrenal cortical cells, and others) are capable of interacting with specific plasma lipoproteins. In studying these processes, our attention has been focused on the protein moieties of the lipoproteins as the determinants responsible for the interaction with cells. These studies have relied on the use of various plasma lipoproteins which have specific lipid and apoprotein constituents. Low-density lipoproteins (LDL) from various species, including man, contain almost exclusively the B apoprotein. Another useful class of lipoproteins with a lipid composition and particle size similar to those of LDL has been identified in the plasma of various animals. These lipoproteins, which are related to high-density lipoproteins (HDL), are referred to as HDL, and HDL, in control and cholesterol-fed dogs, rats, and swine, respectively.1-6 The HDL, and HDL, occur, in part, in the low-density range, but are distinctly different from LDL in that they lack the B apoprotein. They contain the E and A-I apoproteins or exclusively the E apoprotein, the latter is referred to as apoE HDL,. Such lipoproteins are present in human plasma, and their concentration appears to increase after cholesterol feeding.6,' The role of specific apoproteins has been studied by comparing the metabolism, in vitro and in vivo, of these particular lipoproteins, including LDL containing the B apoprotein, HDL, containing exclusively the E apoprotein (apoE HDL,), and HDL containing primarily the A-I (or A-I and A-11) apoprotein without the E apoprotein. Selective chemical modification of lysine and arginine residues of these lipoproteins has been used to probe the nature of lipoprotein cell interactions in vitro in cultured cells and in vivo in various animals after intravenous injection.