有机阴离子转运体研究的最新进展

Research advances in organic anion transporter

有机阴离子转运体(organic anion transporter,OAT)亚家族是溶质转运体22(solute carrier 22,SLC22)家族中的重要组成部分,在包括肝脏、肾脏、脑及胎盘等在内的多种组织脏器中表达。因其能够介导许多常见药物(抗生素、抗病毒药、利尿药和非甾体类抗炎药)、毒素以及营养物质在机体内的排泄而受到了广泛的关注。近年来,在Oat1和Oat3基因敲除鼠的代谢组学和微阵列数据以及系统生物学的研究表明,OAT通路在处理肠道微生物代谢和肾脏疾病状态下发挥着非常重要的作用。核受体和其他转录因子会与Ⅰ相和Ⅱ相药物代谢酶结合并调节特定OATs的表达。"远端遥感和信号通路假说"表明,OATs能在许多组织中表达并且转运多种信号分子。一些OATs对于特定的信号分子,如环核苷酸、尿酸和前列腺素等还具有高度的选择性,因此可以有效的介导多种器官、组织及细胞间的信息交流。OATs在正常情况及急慢性病理条件下,在内外源物的转运中起到重要作用。

The organic anion transporter（OAT） subfamily is an important part of the SLC22（solute carrier 22） transporter family. OATs are expressed in many tissues, including liver, kidney, brain, placenta and so on. A great deal of attention has been paid to OAT because of its role in handling of common drugs（antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs）, toxins and nutrients. Data from recent metabolomics, microarray and system biology studies, phenotypes of Oat1 and Oat3 knockouts, indicate a central role of this pathway in the metabolism as well as putative uremic toxins of kidney disease. The expressions of certain OATs in conjunction with phase I and phase II drug metabolizing enzymes are regulated by nuclear receptors and other transcription factors. According to the ＂remote sensing and signaling hypothesis＂, some OATs have a strong relationship with certain particular signaling molecules. OATs may play a role in remote inter-organ communication via regulating levels of signaling molecules and key metabolites in tissues and body fluids. OATs play a significant role in the transportation of internal and external material under normal and pathological conditions.