Klemm A R, Young D, Lloyd J B
Division of Developmental Biology, Jefferson Medical College, Alfred I. Dupont Hospital for Children, Wilmington, DE 19899, USA.
Biochem Pharmacol. 1998 Jul 1;56(1):41-6. doi: 10.1016/s0006-2952(98)00098-7.
Polyethyleneimine (PEI) is shown to destabilize isolated rat liver lysosomes, as indicated by a decrease in the latency of their acid N-acetyl-beta-glucosaminidase. PEI also inhibited the generation of radiolabeled digestion products from 125I-labeled bovine serum albumin endocytosed by rat visceral yolk sac in vitro. However, PEI did not greatly inhibit the endocytic uptake of a nondigestible fluid-phase substrate, fluorescein isothiocyanate (FITC)-dextran. It is hypothesized that PEI inhibits the adsorptive endocytosis of 125I-labeled bovine serum albumin, and thus its subsequent intralysosomal digestion, by competing with and displacing the labeled protein from its binding sites on the visceral yolk sac cell surface. This hypothesis suggests a plausible explanation for the ability of PEI to act as an efficient vector for gene and oligonucleotide transfer into mammalian cells. PEI present in the culture medium is carried into cells by adsorptive endocytosis. Concentrated thus on the endosome membrane, it permeabilizes this membrane and so affords DNA conjugated to the PEI an otherwise unavailable mode of access into the cytoplasm.
聚乙烯亚胺（PEI）可使分离的大鼠肝脏溶酶体不稳定，这可通过其酸性N-乙酰-β-氨基葡萄糖苷酶潜伏期的缩短来表明。PEI还抑制了大鼠内脏卵黄囊体外摄取的125I标记牛血清白蛋白产生放射性标记的消化产物。然而，PEI对不可消化的液相底物异硫氰酸荧光素（FITC）-葡聚糖的内吞摄取没有很大抑制作用。据推测，PEI通过与标记蛋白竞争并将其从内脏卵黄囊细胞表面的结合位点上置换下来，从而抑制125I标记牛血清白蛋白的吸附性内吞作用，进而抑制其随后的溶酶体内消化。这一推测为PEI作为基因和寡核苷酸导入哺乳动物细胞的有效载体的能力提供了一个合理的解释。培养基中的PEI通过吸附性内吞作用进入细胞。因此浓缩在内体膜上，它使该膜通透性增加，从而为与PEI偶联的DNA提供了一种进入细胞质的原本无法获得的途径。
