Laboratory of Immunochemistry and Ultrastructure, Institute of Anatomy, Central University of Venezuela, Caracas, Venezuela.
Department of Physiology I, University of Tubingen, Tubingen, Germany.
Biochim Biophys Acta Biomembr. 2017 May;1859(5):679-685. doi: 10.1016/j.bbamem.2017.01.011. Epub 2017 Jan 10.
The boron element possesses a range of different effects on living beings. It is essential to beneficial at low concentrations, but toxic at excessive concentrations. Recently, some boron-based compounds have been identified as promising molecules against Trypanosoma brucei, the causative agent of sleeping sickness. However, until now, the boron metabolism and its access route into the parasite remained elusive. The present study addressed the permeability of T. brucei aquaglyceroporins (TbAQPs) for boric acid, the main natural boron species. To this end, the three TbAQPs were expressed in Saccharomyces cerevisiae and Xenopus laevis oocytes. Our findings in both expression systems showed that all three TbAQPs are permeable for boric acid. Especially TbAQP2 is highly permeable for this compound, displaying one of the highest conductances reported for a solute in these channels. Additionally, T. brucei aquaglyceroporin activities were sensitive to pH. Taken together, these results establish that TbAQPs are channels for boric acid and are highly efficient entry pathways for boron into the parasite. Our findings stress the importance of studying the physiological functions of boron and their derivatives in T. brucei, as well as the pharmacological implications of their uptake by trypanosome aquaglyceroporins.
硼元素对生物具有一系列不同的影响。在低浓度下是必需的，而在高浓度下则是有毒的。最近，一些基于硼的化合物已被确定为对抗昏睡病病原体——布氏锥虫的有前途的分子。然而，到目前为止，硼的代谢及其进入寄生虫的途径仍然难以捉摸。本研究探讨了 T. brucei 水通道蛋白（TbAQPs）对硼酸的通透性，硼酸是主要的天然硼物种。为此，将三种 TbAQPs 在酿酒酵母和非洲爪蟾卵母细胞中进行了表达。我们在这两个表达系统中的发现表明，所有三种 TbAQPs 对硼酸都具有通透性。特别是 TbAQP2 对这种化合物具有很高的通透性，显示出这些通道中报道的最高溶质电导率之一。此外，T. brucei 水通道蛋白的活性对 pH 值敏感。综上所述，这些结果表明 TbAQPs 是硼酸的通道，并且是硼进入寄生虫的高效进入途径。我们的发现强调了研究硼及其衍生物在 T. brucei 中的生理功能以及它们被锥虫水通道蛋白摄取的药理学意义的重要性。
