Fakla I, Hever A, Molnár J, Fischer J
Department of Biochemistry, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Anticancer Res. 1998 Jul-Aug;18(4C):3107-11.
Two main isoforms of P-glycoproteins can be distinguished according to their solubility in ionic and non-ionic detergents. Studies on mdr cell lines and brain capillary vessels support the evidence that tomato lectin reveals high affinity binding to the oligosaccharide chains of the SDS soluble isoform of P-glycoprotein, but not to the non-ionic detergent soluble isoform. Thus the SDS-soluble isoform represents a glycoform having polylactosamines in its oligosaccharide chains. The function of these oligosaccharides is still unknown, although the carbohydrate chains of P-glycoprotein were believed to take part in correct protein folding only. We also demonstrated that lectin binding to the extracellular lactosamine sequences of drug efflux pump does not change its efficiency on mdr cell lines, but interferes with the inhibitory action of some drugs, such as verapamil and promethazine. In accordance with earlier findings we assume that carbohydrate chains might be involved in stabilization of the active conformation of efflux pump. The possible role of lectin treatment in maintaining P-glycoprotein mediated blood-brain barrier functions has to be proved in further investigations.
根据P-糖蛋白在离子型和非离子型去污剂中的溶解性，可以区分出两种主要的同工型。对多药耐药细胞系和脑微血管的研究支持了以下证据：番茄凝集素与P-糖蛋白的SDS可溶性同工型的寡糖链具有高亲和力结合，但与非离子型去污剂可溶性同工型没有结合。因此，SDS可溶性同工型代表一种在其寡糖链中具有多聚乳糖胺的糖型。这些寡糖的功能仍然未知，尽管人们认为P-糖蛋白的糖链仅参与正确的蛋白质折叠。我们还证明，凝集素与药物外排泵的细胞外乳糖胺序列结合不会改变其在多药耐药细胞系上的效率，但会干扰某些药物（如维拉帕米和异丙嗪）的抑制作用。根据早期的研究结果，我们推测糖链可能参与外排泵活性构象的稳定。凝集素处理在维持P-糖蛋白介导的血脑屏障功能中的可能作用必须在进一步的研究中得到证实。
