Prehm Peter, Schumacher Udo
Muenster University Hospital, Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstrasse 15, D-48149 Münster, Germany.
Biochem Pharmacol. 2004 Oct 1;68(7):1401-10. doi: 10.1016/j.bcp.2004.06.017.
In a previous report we described the export of hyaluronan from Streptococcus pyogenes by an ABC transporter. Extending these findings a sequence homology search against human proteins revealed a strong homology to the multidrug resistance transporter ABC-B (MDR-1) and ABC-C (MRP 5). Using several inhibitors directed against these and other transporters, a decreased hyaluronan production in cell culture as well as in hyaluronan synthase activity in purified membrane fractions was observed. The inhibitory capacity (IC(50) concentrations) was compared the with reported IC(50)- or the K(i)-concentrations for individual transporters. These analyses revealed that hyaluronan is synthesized within the cytoplasm of mammalian cells and actively secreted into the pericellular space by energy dependent transport proteins. While inhibition of several transport proteins resulted in a decrease of hyaluronan export, inhibition of the MRP5 transporter was the most effective one to decrease hyaluronan in the cell culture supernatant indicating that hyaluronan export is one physiological role of this transport protein.
在之前的一份报告中，我们描述了化脓性链球菌通过ABC转运蛋白输出透明质酸的过程。拓展这些发现，针对人类蛋白质进行的序列同源性搜索显示，其与多药耐药转运蛋白ABC - B（MDR - 1）和ABC - C（MRP 5）具有很强的同源性。使用几种针对这些及其他转运蛋白的抑制剂，在细胞培养中观察到透明质酸产量降低，在纯化的膜组分中透明质酸合酶活性也降低。将抑制能力（IC(50)浓度）与各转运蛋白报道的IC(50)或K(i)浓度进行比较。这些分析表明，透明质酸在哺乳动物细胞的细胞质中合成，并通过能量依赖的转运蛋白主动分泌到细胞周隙。虽然抑制几种转运蛋白会导致透明质酸输出减少，但抑制MRP5转运蛋白对降低细胞培养上清液中的透明质酸最为有效，这表明透明质酸输出是该转运蛋白的一种生理功能。
