Kim Sun-Mee, Park Tae-Won, Park Jin-Woo
Department of Biochemistry, Chonbuk National University Medical School, Jeonju 561-756, Republic of Korea.
J Biochem Mol Biol. 2002 Sep 30;35(5):518-23. doi: 10.5483/bmbrep.2002.35.5.518.
Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, inhibits the secretion of proteins and causes the redistribution of resident Golgi proteins into the endoplasmic reticulum (ER). In this study, the effect of NDGA on lipoprotein lipase (LPL) secretion was investigated in 3T3-L1 adipocytes, and compared with those of brefeldin A (BFA), a well-known fungal metabolite that exhibits similar ER-Golgi redistribution. Both BFA and NDGA blocked secretions of LPL. In the presence of BFA, the active and dimeric LPL was accumulated in adipocytes. After endoglycosidase H (endo H) digestion, the proportion of LPL subunits with partially endo H-sensitive oligosaccharide was significantly increased with BFA. However, in the presence of NDGA, the cellular LPL became inactive, and only the endo H-sensitive fraction of the LPL subunit was observed. An increase of the aggregated forms was observed in the fractions of the sucrose-density gradient ultracentrifugation. These properties of LPL in the NDGA-treated cells were similar to those of LPL that is retained in ER, and the effects of NDGA could not be reversed by BFA. These results indicate that the inhibitory mechanism of NDGA on the LPL secretion is functionally different from the ER-Golgi redistribution that is induced by BFA.
去甲二氢愈创木酸（NDGA）是一种脂氧合酶抑制剂，它能抑制蛋白质分泌，并导致驻留高尔基体蛋白重新分布到内质网（ER）中。在本研究中，研究了NDGA对3T3-L1脂肪细胞中脂蛋白脂肪酶（LPL）分泌的影响，并与布雷菲德菌素A（BFA）进行了比较，BFA是一种著名的真菌代谢产物，具有类似的内质网-高尔基体重新分布现象。BFA和NDGA均阻断了LPL的分泌。在BFA存在的情况下，活性和二聚体形式的LPL在脂肪细胞中积累。经内切糖苷酶H（endo H）消化后，BFA处理使具有部分endo H敏感寡糖的LPL亚基比例显著增加。然而，在NDGA存在的情况下，细胞内的LPL变得无活性，仅观察到LPL亚基的endo H敏感部分。在蔗糖密度梯度超速离心的组分中观察到聚集形式增加。NDGA处理细胞中LPL的这些特性与保留在内质网中的LPL相似，并且BFA不能逆转NDGA的作用。这些结果表明，NDGA对LPL分泌的抑制机制在功能上不同于BFA诱导的内质网-高尔基体重新分布。
