Lee Young Hwan, Kang Hye-Min, Kim Min-Sub, Lee Jin-Sol, Jeong Chang-Bum, Lee Jae-Seong
Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419, South Korea.
Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419, South Korea; Department of Chemistry, College of Natural Sciences, Dongduk Women's University, Seoul 02748, South Korea.
Aquat Toxicol. 2018 Feb;195:129-136. doi: 10.1016/j.aquatox.2017.12.016. Epub 2017 Dec 30.
P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are ATP-binding cassette (ABC) transporters that confer multixenobiotic resistance (MXR) via their efflux activity, which enables a variety of xenobiotics to be expelled from cells. MXR has been proposed as the first line of defense against xenobiotics. In this study, the protective roles of P-gp and MRP in the rotifer Brachionus koreanus were examined in response to four biocides (alachlor, chlorpyrifos, endosulfan, and molinate) using fluorescent substrates and inhibitors specific to P-gp and MRP. Exposure of rotifers to the four biocides resulted in increased P-gp and MRP activity. Moreover, the rotifers became more sensitive to the biocides with a reduced tendency in survival and slower population growth rates, when P-gp or MRP was inhibited. These findings suggest that P-gp and MRP are involved in the defense system in response to biocide exposure. Furthermore, the transcriptional levels of the genes encoding P-gp and MRP were examined to uncover the mechanism by which MXR is regulated. Our results demonstrate a crucial role of the MXR efflux system in the defense response to biocides, thereby providing a better understanding of rotifer defense mechanisms on the molecular level.
P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP)是ATP结合盒(ABC)转运蛋白,它们通过外排活性赋予多异生物质抗性(MXR),使多种异生物质能够从细胞中排出。MXR被认为是抵御异生物质的第一道防线。在本研究中,使用P-gp和MRP特异性的荧光底物和抑制剂,研究了P-gp和MRP在轮虫韩国臂尾轮虫中对四种杀生物剂(甲草胺、毒死蜱、硫丹和禾草敌)的保护作用。轮虫暴露于这四种杀生物剂导致P-gp和MRP活性增加。此外,当P-gp或MRP受到抑制时,轮虫对杀生物剂变得更加敏感,存活趋势降低,种群增长率减慢。这些发现表明P-gp和MRP参与了对杀生物剂暴露的防御系统。此外,检测了编码P-gp和MRP的基因的转录水平,以揭示MXR的调控机制。我们的结果证明了MXR外排系统在对杀生物剂的防御反应中的关键作用,从而在分子水平上更好地理解轮虫的防御机制。