Jessup W, Mander E L, Dean R T
Heart Research Institute, Sydney, Australia.
Biochim Biophys Acta. 1992 Jun 22;1126(2):167-77. doi: 10.1016/0005-2760(92)90287-6.
We have studied the effect of several chemical modifications to low-density lipoprotein (LDL) on its intracellular fate in macrophages. Native, acetylated and oxidized 125I-LDL were supplied to cultured peritoneal macrophages and the accumulation and distribution of labelled protein was measured both during uptake and a subsequent chase period. The intracellular accumulation of macromolecular oxidized LDL protein greatly exceeded that of acetylated LDL, despite similar rates of uptake and common endocytic receptors. The accumulation of intracellular apoprotein was proportional to the extent to which the LDL was first oxidized. ApoB of oxidized LDL was more resistant to proteolysis by lysosomal enzymes than native apoB. Interestingly, acetylated apoB is more rapidly hydrolysed than the native protein. 125I-LDL modified with 4-hydroxynonenal (HNE) and myricetin, but not with malondialdehyde (MDA), was also accumulated within macrophages in a high-molecular weight fraction, and was resistant to cell-free lysosomal proteolysis. These forms of LDL also contained crosslinked apoB molecules. It is suggested that the accumulation of oxidized LDL within macrophages may he due, at least in part, to the formation of inter- or intra-molecular crosslinks in apoB which render it less accessible to proteolysis.
我们研究了对低密度脂蛋白（LDL）进行几种化学修饰后对其在巨噬细胞内命运的影响。将天然、乙酰化和氧化的¹²⁵I-LDL提供给培养的腹膜巨噬细胞，并在摄取期间和随后的追踪期测量标记蛋白的积累和分布。尽管摄取速率相似且具有共同的内吞受体，但大分子氧化LDL蛋白的细胞内积累大大超过了乙酰化LDL。细胞内载脂蛋白的积累与LDL首先被氧化的程度成正比。氧化LDL的载脂蛋白B比天然载脂蛋白B对溶酶体酶的蛋白水解更具抗性。有趣的是，乙酰化载脂蛋白B比天然蛋白水解得更快。用4-羟基壬烯醛（HNE）和杨梅素修饰而非丙二醛（MDA）修饰的¹²⁵I-LDL也以高分子量部分在巨噬细胞内积累，并且对无细胞溶酶体蛋白水解具有抗性。这些形式的LDL还含有交联的载脂蛋白B分子。有人提出，巨噬细胞内氧化LDL的积累可能至少部分是由于载脂蛋白B中分子间或分子内交联的形成，这使得它不易被蛋白水解。
